Category Archives: Gene Medicine

Glimpse of Health Care Player CSLs Gene Therapy

Wait, What? $2.1 million for just a drug? Yes, you heard it right!

Few months back in Belgium, a fundraising campaign was held to raise funds to pay for a one-time gene-therapy of a toddler suffering from an extremely rare spinal muscular atrophy (SMA)disorder. What has caught everyones attention, was the astonishing $2.1 million price of the drug. The question here is whether it is worth?

What is Gene Therapy?

First lets understand what gene therapy is. Gene therapy is one of the most cutting-edge medical technologies, possessing an untold potential on the brink of revolutionizing the treatment of most debilitating, rare and genetic ailments.

In gene therapy, the expression of a patients genes is modified either by deactivating/blocking or repairing the defective genes, and resuming their normal function, thereby, offering a novel and unique approach for treating life-long and devastating diseases.

One-off gene therapy is a one-time treatment, or a single dose/injection or infusion treatment given to patients.

Prices and One-off Gene Therapy

Although these novel gene therapies present significant advantages to patients with unmet medical needs and have been gaining a lot of praise for their innovative way of disease treatment, but they come at a skyrocket price. For instance,

Such high prices of drugs have ignited debate amid companies (those developed them), stakeholders, and patients.

Payers are still struggling to find out the long-term repercussions of these novel and expensive treatment options that may possibly succeed in addressing and curing disease in just a single dose.

But the companies who have developed these drugs are defending the record-breaking cost of the medicine, arguing that such treatments are still cheaper than the alternate treatment available in the market.

Life-time advantage squeezed down to one-time treatment -Zolgensma Vs Spinzara

There has been a recent fuss in the market when the leading biotech company Novartis joined the debate and defended Zolgensma high price that cures SMA which is a leading cause of mortality in a newborn, emphasizing on the fact that the one-time treatment is more valuable than the costly long-run treatments.

Novartis stated an example of its rival drug Spinraza (an alternative treatment to spinal muscular atrophy, developed by Biogen), which requires infusion in every 4 years at a price of $750,000 in the first year and a maintenance dose of $375,000 per year thereafter.

Me Lennon further emphasized that considering the alternate therapy costs $4 million over a span of ten years, while the one-time cost of Zolgensma is $2.1 million, designating Zolgensma the worlds most expensive drug is deceptive.

Connecting the dots-Reducing Financial Burden

Nevertheless, these novel and costly therapies have intensified the discussions on placing a value on gene therapy and how the government and the health care systems can aid in upfront payment for these one-off treatments.

Shedding light on this, Mr Lennon informed that the company is undergoing discussions with the government bodies and the health insurers for creating new payment models rendering the substantial cost reasonable for payers. With respect to this, a five-year payment plan has already been proposed by the company.

Stakeholders must come up with innovative approaches to price and reimburse the expensive treatment in order to enhance the patient access to these life-changing, novel gene therapies.

Moreover, to realizing the tremendous potential value gene therapies possesses, a reasonable access for all patients is important and so a flexible thinking about evaluating their value.

Key Players

A range of biotech companies have been leading the market leveraging gene therapy approaches while some drugs have entered the pharmaceutical market. Some are listed below-

Let us now have a glimpse of an Australian biotech player that had expanded its technology platform with gene therapy.

CSL limited (ASX: CSL)

Leading Australian Biotech Giant- CSL limited (ASX: CSL) is focused ondeveloping, manufacturing and commercialising novel protein-based pharmaceuticals, cell-culture media & human plasma fractions, with its two key businessesCSL Behring and Seqirus.

CSL has ventured into gene therapy in the fiscal year 2018 after acquiring Calimmune Inc, in 2017 that provide CSL a new technology platform and manufacturing process.

The Company acquired 100% of the Calimmune Incs equity, by making an upfront fee of $82 million and subsequent contingent payments subject to the achievement of development milestones.

Calimmune is a U.S. biotechnology company that has established a suite of gene therapy technologies with a potential to treat rare diseases.

CSLs in-vivo versus ex-vivo cell and gene therapy (Source: Company Presentation)

CSL gene therapy targets Sickle Cell Disease (CSL200), with high unment need and immune deficiencies such as Wiskott-Aldrich Syndrome (WAS).

Two year post the acquisition of Calimmune, CSL has completed the integration of this new technology into R&D with its first clinical program enrolling patients. CSL also has early stage gene therapy projects under pipeline.

On 13 December 2019, CSLs stock traded at $278.12, down 0.38%. The market cap of the company was noted at $126.72 billion with 453.87 million outstanding shares. The stock has a P/E ratio of 46.22x, with 0.95% of annual dividend yield.

Disclaimer

This website is a service of Kalkine Media Pty. Ltd. A.C.N. 629 651 672. The website has been prepared for informational purposes only and is not intended to be used as a complete source of information on any particular company. Kalkine Media does not in any way endorse or recommend individuals, products or services that may be discussed on this site. Our publications are NOT a solicitation or recommendation to buy, sell or hold. We are neither licensed nor qualified to provide investment advice.

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Continued here:
Would you pay $2.1 million for one-off gene therapy? - Kalkine Media

Every minute of every day our bodies are bombarded with millions of different molecules that we breathe, eat and touch including bacteria, viruses, chemicals and seemingly harmless compounds like food and pollen.

For every one of these encounters, our immune system has to decide if the substance is a threat or not, if it is foreign or self and how the body should respond to stay healthy. To do this, we rely on two immune systems working in tandem.

Scientists have discovered a new human autoinflammatory disease that results from a mutation in an important gene in one of these systems.

The syndrome, now known as CRIA (cleavage-resistant RIPK1-induced autoinflammatory) syndrome causes recurring episodes of debilitating and distressing fever and inflammation.

Read more

Our bodys first line of defence is the innate immune system that is effectively a hard wired and fast response, explains Dr Najoua Lalaoui from the Walter and Eliza Hall Institute of Medical Research (WEHI) and the Department of Medical Biology at the University of Melbourne.

This system works in the skin and mucous membranes like the mouth, making sure that any invaders like bacteria are detected and destroyed quickly, she says.

If pathogens do enter the body, the innate immune cells move to the site of infection and physically devour invaders and activate chemical messengers to alert the body.

This can lead to an inflammatory reaction where blood circulation is increased, the affected area becomes swollen and hot, and the person may experience fever. When these chemical messengers are over-active it can result in conditions like colitis, arthritis and psoriasis.

Supporting this system is the adaptive immunity system that involves antibodies that recognise and then train the body to respond to threats. This is our memory immunity and the basis of how vaccinations work.

Scientists from the WEHI, with colleagues at the National Institutes of Health (NIH) in the United States, have been working to understand why patients from three families suffered from a history of painful swollen lymph nodes, fever and inflammation.

The families had a range of other inflammatory symptoms which began in childhood and continued into their adult years.

Read more

This type of repeated fever often indicates an issue with the innate immune system and the same disease in an extended family can indicate genetic changes that are passed from parents to their children, explains Dr Lalaoui.

Previous tests didnt identify any known cause.

But by sequencing the patients genomes, the NIH team identified a mutation in DNA that codes for a molecule known as RIPK that they suspected might cause the disease.

RIPK is a critical regulator of inflammation and the cell death pathway responsible for cleaning up damaged cells or those infected by pathogens.

Professor John Silke from the Walter and Eliza Hall Institute and his team have been studying RIPK1 for more than 10 years. His team had previously shown that damaging the RIPK1 gene could lead to uncontrolled inflammation and cell death.

RIPK1 is a potent controller of cell death, which means cells have had to develop many ways of regulating its activity, Professor Silke says.

In this paper, we showed that one way that the cell regulates its activity is by cleaving RIPK1 into two pieces to disarm the molecule and halt its role in driving inflammation.

In this condition (CRIA), the mutations are preventing the molecule from being cleaved into two pieces, resulting in autoinflammatory disease. This helped confirm that the mutations identified by the NIH researchers were indeed causing the disease, he says.

Read more

He explains that mutations in RIPK1 can drive both too much inflammation as in autoinflammatory and autoimmune diseases and too little inflammation, resulting in immunodeficiency.

There is still a lot to learn about the varied roles of RIPK1 in cell death, and how we can effectively target RIPK1 to treat disease.

In CRIA syndrome, the mutation in RIPK1 overcomes all of the normal checks and balances that exist, resulting in uncontrolled cell death and inflammation, says Dr Steven Boyden from the National Human Genome Research Institute at the NIH.

Dr Boyden says the first clue that the disease was linked to cell death was when they delved into the patients exomes the part of the genome that encodes all of the proteins in the body.

The team sequenced the entire exome of each patient and discovered unique mutations in the exact same amino acid of RIPK1 in each of the three families.

It is remarkable, like lightning striking three times in the same place. Each of the three mutations has the same result it blocks cleavage of RIPK1 which shows how important RIPK1 cleavage is in maintaining the normal function of the cell, says Dr Boyden.

Dr Lalaoui said the WEHI researchers then confirmed the link between the RIPK1 mutations and CRIA syndrome in laboratory models.

Read more

We showed that mice with mutations in the same location in RIPK1 as in the CRIA syndrome patients, had a similar exacerbation of inflammation, she says.

Dr Dan Kastner from NIH widely regarded as the father of autoinflammatory disease says colleagues had treated CRIA syndrome patients with a number of anti-inflammatory medications, including high doses of corticosteroids and biologics, compounds that block specific parts of the immune system.

And although some of the patients markedly improved, others responded less well or had significant side effects.

Understanding the molecular mechanism by which CRIA syndrome causes inflammation provides an opportunity to get right to the root of the problem, Dr Kastner says.

Dr Kastner noted that RIPK1 inhibitors, which are already available on a research basis, may provide a focused, precision medicine approach to treating patients.

RIPK1 inhibitors may be just what the doctor ordered for these patients. The discovery of CRIA syndrome also suggests a possible role for RIPK1 in a broad spectrum of human illnesses, such as colitis, arthritis and psoriasis.

Banner: WEHI

The rest is here:
The genetic mutation behind a new autoinflammatory disease - Pursuit

An American biotech company has launched clinical trials in Colombia to test a new therapy designed to reverse the aging process, and in turn, treat age-related diseases, according to news reports.

But to steal a sip from this purported fountain of youth, participants in the trial must first fork over $1 million a fee that seems even more astronomical when you consider that most clinical trials are either free or provide participants with financial compensation, according to a report by OneZero, a Medium publication about tech and science.

The pricey trial is being run by Libella Gene Therapeutics, a Kansas-based company whose website proclaims that "the future is here." The company announced its intention to test its anti-aging remedies in Cartagena, Colombia, in 2018, and began recruiting for the trials in October of this year. Using a single-gene therapy, Libella aims to "prevent, delay, or even reverse" the general effects of aging, as well as treat diseases that emerge in old age, such as Alzheimer's, according to ClinicalTrials.gov.

In fact, in its own press release, the company boasted, without evidence, that its gene therapy "may be the world's first cure for Alzheimer's disease." The bold claim raises an obvious question: Will the treatment actually work?

Short answer: No one really knows, but the fact that Libella shipped its operation beyond the reach of the U.S. Food and Drug Administration (FDA) doesn't inspire confidence, experts told OneZero.

Related: 5 Reasons Not to Fear Getting Older

Unlike anti-aging face creams that soften the superficial signs of aging, the Libella therapy aims to reverse aging from the ground up, so to speak, starting at the level of our genes. Specifically, the gene therapy is intended to lengthen patients' telomeres structures that cap the tips of chromosomes and prevent the genetic material inside from fraying. Telomeres grow shorter each time a cell divides, and when the structures reach a critical length, cells either stop dividing or perish, according to Stanford Medicine.

The theory goes, if you rebuild the body's shortened telomeres, the process of aging might be thrown in reverse. This is not a new idea. Several studies in mice suggest that using gene therapy to lengthen telomeres can reverse certain signs of aging in the animals. A 2015 study from Stanford prompted similar effects in isolated human cells; the treatment lengthened cells' telomeres by fiddling with a close cousin of DNA, called RNA, which helps cells build proteins.

The Libella therapy aims to help cells rebuild telomeres by activating a gene in their DNA that would normally be switched "off." The gene, called TERT, contains instructions to build a protein called "telomerase," an enzyme that adds molecules to the end of telomeres and prevents the structures from shortening during cell replication, according to a 2010 report in the journal Biochemistry.

Libella's lead scientific officer, molecular biologist William Andrews, originally helped identify the human telomerase enzyme at the biotech firm Geron. Later, he licensed a gene therapy based on the finding to Libella, according to OneZero. "I can't say [telomere shortening is] the only cause of aging, but it plays a role in humans," Andrews told the publication.

Related: 8 Tips for Healthy Aging

Andrews' therapies will soon be put to the test in Colombia, where one 79-year-old will receive the anti-aging treatment in next month, according to OneZero. The anti-aging trial will include four more participants over age 45 and focus on verifying that the treatment is "safe and tolerable," meaning it does not harm patients or cause unacceptable side effects.

Two more trials will use the same therapy but aim to "prevent, delay, or even reverse the development" of Alzheimer's disease and critical limb ischemia, an age-related condition in which a person's arteries become severely obstructed. Participants in these trials must already be diagnosed with the disorders.

After treatment, participants in all three trials will remain in the clinic for 10 days for further monitoring, and then return at regular intervals for checkups over the following year.

Libella's gene therapy involves a one-time injection delivered through an IV; the Alzheimer's therapy uses the same formula but doctors inject the product into the patient's spinal fluid. Within the product, a modified virus carries the TERT gene into cells and injects the genetic material into their DNA. The modified viruses cannot transmit diseases to people, but in high enough doses, the germs could provoke a harmful immune response in the patient, according to a 2018 animal study. Libella representatives declined to say how high a dose their clinical trial participants will receive.

"All I can say is, it's a lot," Andrews told OneZero.

Potential side effects aside, the fact that the Libella treatment will be administered beyond the purview of the FDA is telling, according to one expert. Leigh Turner, a bioethicist at the University of Minnesota, told OneZero that "even though the company is based in the United States, they've managed to find a way to evade U.S. federal law by going to a jurisdiction where it's easier to engage in this activity."

The $1 million entry fee is also alarming, Turner said, given that most clinical trials don't charge patients anything to enter. Andrews told OneZero that the fee is justified because it costs the company hundreds of thousands of dollars to make enough product to treat just one person.

The appearance of the trials on ClinicalTrials.gov, an official registry maintained by the National Institutes of Health, does not boost their credibility, she added. The automated database can be easily manipulated and "can basically be used as a marketing platform," she said.

Other stakeholders in the telomere-lengthening business are concerned, too. Michael Fossel, founder and president of the biotech startup Telocyte, told OneZero that his company's own therapy is similar to the Libella treatment the difference is that Telocyte is seeking approval through the FDA. "We're afraid that something will go wrong [with the Libella trials], whether it's from a safety or efficacy standpoint," he said.

Related: Extending Life: 7 Ways to Live Past 100

But even in a best case scenario, wherein no patients come to harm, the Libella therapy still might not deliver any notable health benefits. Some research suggests that no link exists between telomere length and aging.

For instance, a study published this year examined more than 261,000 people between age 60 and 70, and found no correlation between participants' telomere lengths and their age-related health outcomes, including their overall cognitive function, muscular integrity and the age of their parents. Long telomeres were associated with a lowered risk of coronary heart disease as compared with short telomeres, but longer telomere length was also linked to a heightened risk of cancer.

"Telomere lengthening may offer little gain in laterlife health status" and lead to an increased risk of cancer, the authors noted.

It remains to be seen whether Libella has truly tapped the fountain of youth, but given the dubious nature of their clinical trials, potential participants may want to exercise caution before relocating to Colombia and shelling out $1 million for a chance to live longer.

Originally published on Live Science.

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New Anti-Aging Clinical Trial Begins. For $1 Million, You Can Be a Participant. - Livescience.com

At the annual San Antonio Breast Cancer Symposium, MSK investigators presented the latest research on detection and screening methods for people at high risk;immunotherapy for breast cancer;and the underlying causes of resistance to targeted therapies, among other topics.

Here are some of the noteworthy studies that featured contributions from MSK investigators.

Mammography screening has been shown to reduce breast cancer mortality by about 30% in the general population. But in women at an increased risk for the disease, additional imaging is recommended. This group includes people who carry a BRCA or other genetic mutation. Other risk factors include a family or personal history of breast cancer, certain high-risk lesions, or having undergone chest radiation at a young age.

At SABCS, diagnostic radiologist Maxine Jochelson discussed newer imaging technologies and the advantages they have over mammograms alone for detecting cancer in high-risk women. People in the high-risk group may need supplemental imaging to improve early detection, Dr. Jochelson says.

She explains that this approach would incorporate vascular imaging techniques. These methods can highlight areas of increased blood flow, a hallmark of tumor growth. This technology includes MRI and contrast-enhanced mammography. It can find tumors that mammograms may miss. Although vascular imaging costs more and generally takes longer to perform, its use is justified in high-risk women because ofthe increased chance of finding cancer, she says.

Mammograms & Other Types of Breast Exams

Learn about the different types of breast exams that can help detect breast cancer at its earliest stages, before symptoms develop.

Its undisputed that vascular imaging is better at detecting cancers than purely anatomical imaging, Dr. Jochelson adds. She emphasizes the need to fine-tune imaging strategies based on each persons specific risk factors.

Some of the imaging approaches she discussed during her presentation include:

We need to continue improving ways of assessing an individuals risk so we can stratify them and determine which type of imaging will most benefit each patient, Dr. Jochelson says. The true test will be studies to demonstrate that these newer technologies actually save lives.

Immunotherapy that uses genetically engineered cells, such as chimeric antigen receptor (CAR) T cells, has proven effective in treating some forms of blood cancer. So far, efforts to create immune cells that can effectively target solid tumors, including breast cancer, have been disappointing. At SABCS, MSK physician-scientist Christopher Klebanoff presented research from his lab on a novel tactic for enabling the immune system to better target and kill breast cancer cells while sparing healthy tissue.

We believe a major limiting challenge in successfully developing immunotherapy for breast cancer has been the identification of antigens. These are targets that the immune system can recognize, Dr. Klebanoff explains. Weve become very interested in the possibility that common mutations in breast cancer may produce antigens that can be recognized as foreign by the immune system.

The Klebanoff labs current research focuses on a gene called PIK3CA, which is mutated in about 40 to 45% of hormone receptor-positive breast cancers. It is also mutated in some HER2-positive and triple-negative breast cancers. Mutations inPIK3CA cause cancer cells to grow in an uncontrolled manner. In May 2019, the US Food and Drug Administration approved a pill called alpelisib (Piqray), which targets mutations in this gene. However, the drug has the potential for significant side effects, and tumors ultimately develop resistance to this medicine. Dr. Klebanoff and his colleague Smita Chandran, a senior research scientist in his lab and the scientific lead on this study, decided to look for a way to target antigens created by this mutation using immune cells designed to recognize them.

We believe a major limiting challenge in successfully developing immunotherapy for breast cancer has been the identification of antigens.

A challenging aspect of this approach was that mutated PIK3CA is found on the inside of cancer cells, allowing it to hide from many components of the immune system, such as antibodies. Physiological processes present in all cells, including cancer cells, allow mutated PIK3CA to be broken down into shorter fragments and loaded onto a molecular basket, called HLA, which is shuttled to the surface of the cell, Dr. Klebanoff says. This process allows immune cells to functionally look inside of other cells.

The researchers identified a specialized molecule, known as a T cell receptor, that has the ability to recognize this mutated PIK3CA-HLA complex. Immune cells specific for this complex recognize the target cell as being cancerous and destroy it. Healthy cells without the mutation remain untouched. The T cell receptors are matched to a patients unique complement of HLA molecules. As with a stem cell transplant, HLA must be matched for this immunotherapy to be effective.

Right now we are focused on the most common HLA types that are seen in a large proportion of our patients. The big-picture goal is to build a library of T cell receptors that can work in people with different HLA molecules and can target other common cancer mutations, Dr. Chandran explains. This work is still early and so far has only been done in the laboratory and not in humans. We are nonetheless excited about the prospect of working toward developing a more effective and less toxic immunotherapy customized to the genetic attributes of a patients tumor.

CDK4/6 inhibitors are an important class of drugs to treat estrogen receptor-positive breast cancer. These drugs stop the growth of breast cancer cells by targeting enzymes that are important in cell division. They are given in addition to hormone therapy. But about 10 to 15% of people who get these drugs dont respond to CDK4/6 inhibitors, and others later develop resistance.

MSK physician-scientist Sarat Chandarlapaty has been studying why this is the case. Understanding this resistance could contribute to the development of new targeted drugs. In December 2018, he published a study that reported on two genes that play a critical role in promoting this resistance. At SABCS, he presented his latest research on this area.

Weve been delving deeper into the role of these genes, as well as others, to try to understand some of the principles that could guide the next generation of therapies, Dr. Chandarlapaty says. By working out these detailed mechanisms, we will have the tools needed to design more potent and selective inhibitors for these refractory breast cancers.

Dr. Chandarlapaty explains that because tumors outsmart CDK4/6 inhibitors in different ways, he doesnt expect to find a one-size-fits-all approach for new drugs. There are some key principles for why these drugs fail, he says. For some tumors, making a more potent drug of the same general class will work. Other tumors bypass the pathway in a way that renders many of the old therapies weve used ineffective. For them, a completely different approach is needed.

Researchers Identify Why Women May Develop Resistance to a New Class of Breast Cancer Drugs

Clues emerge about why promising new breast cancer drugs sometimes dont work and what might be done about it.

See more here:
Updates from SABCS 2019: Detection and Screening, Immunotherapy Advances, and Therapy Resistance - On Cancer - Memorial Sloan Kettering

The discovery can be a tool to make earlier and better disease predictions, reduce disease progression and improve patient outcomes

A research team led by Queens University Belfast has made a breakthrough discovery around how and why only certain DNA elements are chosen to regulate gene expression within the vast genome and how this predisposes us to diseases. This new information could help predict a persons risk for various diseases, such as cancer, diabetes and heart disease, and could lead to earlier diagnosis before signs and symptoms of the disease appear.

The research results have been published in the interdisciplinary journaliScience.

Many diseases occur when things go wrong within a cell or set of cells within the body. Previous research has determined that many of these diseases result from mutations on a certain part of the DNA strand, known as an enhancer. Enhancers function as a "turn on" switch in gene expression and activate the promoter region of a particular gene. This means certain genetic traits can be turned on or turned off which in turn shapes a persons early development and lifetime health including their chance of developing a certain disease.

The researchers discovered that enhancer DNA elements exhibit high Propeller Twist (ProT) levels, which is the angle of twisting of two neighbouring DNA bases about their long axis like the propeller blades of an aeroplane.

The research team are the first to discover that because of high ProT levels, the surface of these enhancer sections on the DNA strands are more physically accessible and flexible than its counterparts, thus allowing easier access for DNA binding regulatory proteins. The same properties potentially make these enhancer regions more prone to be affected by mutagenic agents to harm cells and cause certain diseases, such as cancer.

Dr Vijay Tiwari, Reader at Wellcome-Wolfson Institute for Experimental Medicine at Queens University Belfast and lead author on the paper said: These findings answer many fundamental biological questions around the function of DNA in health and disease."

Dr Tiwari explains: It is important to understand how a healthy cell develops to be able to decode what goes wrong in diseases. Our study is the first of its kind to provide insight into the role physical DNA features play in the proper development of specific cell types of the body and how their malfunctions may underlie diseases.

Remarkably, the researchers also discovered that as cells become abnormal, they switch to using low ProT regions as enhancer elements. These observations open novel avenues to understand the aetiology of human diseases and potentially develop an early diagnosis.

Commenting on his findings, Dr Tiwari continues: This could mean we could look at the enhancer section of DNA in any cell of a healthy person and predict their chance of developing disease long before signs and symptoms appear. This could result in many lives being saved as we can use this tool to make earlier and better disease predictions, reduce disease progression and improve patient outcomes.

The classical methods to identify enhancers have been cumbersome. These new findings argue that high ProT levels are a deterministic feature of enhancers. Hence, the researchers hope this discovery will also save resources and time for scientists across the globe in identifying these gene regulatory elements critical in normal as well as diseased states.

The research was carried out in collaboration with researchers from the Ludwig Maximilian University of Munich in Germany.

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Researchers unfold genetic code that controls cell function and disease - BSA bureau

Without modern medicine chances are you'd be dead before 40, new research has found.

Scientists in Australia say the "natural" human lifespan is just 38 - the age Britney Spears is right now, and less than half the 81 years the average New Zealander can expect from the day they're born.

They figured this out by looking at DNA from 262 different species, and how long they're known to live. Using this data, they have been able to work out the lifespans of extinct species - including early humans such as Neandarthals and Denisovans.

"Using the known lifespans of 262 different vertebrate species, we were able to accurately predict lifespan from the density of DNA methylation occurring within 42 different genes," said Ben Mayne of Australia's CSIRO research institute.

"There are many genes linked to lifespan, but differences in the DNA sequences of those genes doesn't seem to explain differences in lifespan between different species.

"Instead, we think that the density of a special type of DNA change called DNA methylation, determines maximum natural lifespan in vertebrates. DNA methylation does not change a gene's sequence but helps control whether and when it is switched on."

Using this knowledge, they worked out that early modern humans - the same as us, anatomically - would have lived about 38 years. This is about the same as other early human species, such as Denisovans and Neandarthals.

Read more:
Our shockingly short lives without modern medicine revealed - Newshub

Nine months after receiving an infusion of gene-edited stem cells, a patient in a closely followed clinical study is free from the blood transfusions necessary for those who live with severe beta-thalassemia, an inherited disease caused by defective red blood cells.

Another patient has not suffered a painful sickle cell crisis in the four months since receiving the same gene-editing therapy in a separate trial for the related blood condition.

The results, unveiled Tuesday by partners CRISPR Therapeutics and Vertex, offer an initial glimpse at the potential for CRISPR-based gene editing to change the course of hereditary disorders like sickle cell and beta-thalassemia.

"This is a very important landmark, not just for us as a company but for the field," said CRISPR CEO Samarth Kulkarni in an interview.

The two patients are the first to be treated in the companies' Phase 1/2 trials, which are the furthest along among drugmaker-led efforts to translate the breakthrough science into medicines and, possibly, genetic cures.

Only so much can be drawn from their experience, and side effects remain a concern in a field that's advanced rapidly from laboratory and animal testing into humans. Fuller data will also be needed to assess if patients improve over time, and remain transfusion- or crisis-free.

But Vertex and CRISPR Therapeutics report that their therapy, dubbed CTX001, appears to have accomplished what it was designed to do. Both patients achieved levels of hemoglobin the oxygen-carrying protein rendered dysfunctional by sickle cell disease and beta-thalassemia that approach what's considered normal, or at least mildly anemic.

Tuesday's disclosure was highly anticipated, both for its implications for gene-editing therapies and as the first clinical update from CRISPR Therapeutics, a Switzerland-headquartered biotech that went public in the U.S. three years ago.

Progress from CRISPR's pipeline also comes as Vertex, which inked a research deal with the smaller drugmaker in 2015, expands beyond the cystic fibrosis research for which it's known. Bets in newer technologies like CRISPR and cell therapy look to play a part in that plan.

CTX001is built from stem or progenitor cells extracted from each patient scheduled to be treated. Those cells are then genetically modified outside the body using CRISPR-cas9technology to spur production of a type of hemoglobin that's present at birth but normally replaced shortly thereafter.

Put simpler, CRISPR and Vertex hope to recreate a condition known as hereditary persistence of fetal hemoglobin, substituting the usually short-lived fetal hemoglobin for the mutant beta-globin found in sickle cell and beta-thalassemia patients.

In the first patient with beta-thalassemia, total hemoglobin reached 11.9 grams per deciliter, of which 10.1 was classified as fetal, at nine months post treatment.According to the World Health Organization, mild anemia is classified as over 11 g/dL and normal as over 13 g/dL.

Prior to enrolling in the study, the individual needed more than one blood transfusion per month. After nine months following treatment without a single transfusion, CRISPR and Vertex said the patient is now transfusion independent.

The sickle cell patient, whose medical journey has been chronicled by NPR, achieved 11.3 g/dL of hemogobin 47% fetal at four months. While she experienced seven vaso-occlusive crises annually in the two years prior to treatment, the individual has yet to have one of the characteristic pain crises since CTX001 infusion.

"The ratio [between sickling, anti-sickling cells] is what matters in sickle cell to prevent sickle cell formation," said CRISPR's Kulkarni, noting that the study's main goal is the proportion of patients whose levels of fetal hemoglobin surpass 20%.

Both patients experienced serious side effects, albeit ones judged by investigators to be unrelated to treatment.

The first experienced pneumonia in the presence of neutropenia and veno-occlusiveliver disease that was linked to the chemotherapy pre-conditioning given before infusion of the gene-edited stem cells.The other reported sepsis occurring alongside neutropenia, gallstones and abdominal pain.

All events resolved, Vertex and CRISPR said.

Both the beta-thalassemia and sickle cell studies began last fall and are each set to enroll as many as 45 patients across sites in the U.S., Canada and Europe.

Enrollment and treatment have proceeded slowly, allowing for the companies to carefully monitor patient safety. The Food and Drug Administration, which previously placed a since-lifted clinical hold on CTX001 in sickle cell disease, has also taken a cautious view of gene-editing therapies.

Once CRISPR and Vertex treat two patients in each study, they anticipate moving more quickly. Further data will be presented at a medical meeting next year, Kulkarni said.

Sickle cell and beta-thalassemia are caused by mutations in the beta-globin gene, leading to the characteristic sickled red blood cells in the former condition and dysfunctional cells in the latter. Anemia, or the resulting insufficient oxygen levels in the blood, can cause organ damage and shorten patients' lifespans.

Both are well understood genetic diseases and now a common target for drugmakershoping to apply advances in gene replacement and gene editing medicine.Biotech developer Bluebird bio, for example, recently won approval in Europe for the gene therapy Zyntegloto treat transfusion-dependent beta-thalassemia, and it hopes to soon expand into sickle cell as well.

Besides Vertex and CRISPR, other drugmakers are advancing CRISPR-based medicines. Editas Medicine, which licenses its intellectual property from a rival academic camp to CRISPR Therapeutics, plans to treat the first patient in a study of its gene-editing candidate for a rare eye disease early next year. A third company, Intellia Therapeutics, is further behind.

Gene editing efforts in academia are progressing, too. Researchers from the University of Pennsylvania recently reported initial findings from the first attempt in the U.S. to use CRISPR gene editing to treat cancer, while in China scientists have moved quickly ahead with testing CRISPR in humans.

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First look at CRISPR, Vertex gene-editing therapy hints at treatment potential - BioPharma Dive

Human-induced pluripotent stem cells (hiPSCs) generated from a persons own adult cells can grow into complex organs that help scientists test drugs or even transplant into patients. However, directing stem cells into forming desired, functional organs in the lab remains challenging.

Now, in a study published in the journal Cell Systems, researchers from Gladstone Institutes in collaboration with Boston University (BU) described using machine learning to better understand how to use CRISPR-Cas9 gene-editing tools to control iPSC organization.

By coaxing these stem cells into forming specific arrangements, the researchers believe they could create functional organs for research or therapeutic purposes.

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While researchers have managed to develop iPSCs into many different cell types but not necessarily functional 3D organs, mainly because they have struggled to manipulate the spatial patterns of stem cells, which define the tissues they eventually grow into. Some have resorted to 3D printing, but it isnt always successful, as cells often migrate away from their printed locations.

Despite the importance of organization for functioning tissues, we as scientists have had difficulty creating tissues in a dish with stem cells, Ashley Libby, a co-first author of the new study, said in a statement. Instead of an organized tissue, we often get a disorganized mix of different cell types.

The researchers previously showed that knocking down two genes, ROCK1 and CDH1, affected the layout of iPSCs in lab dishes. The proteins they encode help regulate interactions between cells, making them ideal candidates to alter the cellular organization of an iPSC group.

But there are so many variables to considerincluding the timing and level of each gene knockdown, the duration and the proportion of cells to work onthat make testing all the combinations by human almost impossible. So, they turned to machine learning for help.

RELATED:Growing transplantable arteries from stem cells

They used a CRISPR-Cas9 gene-editing system that could be triggered by adding the antibiotic doxycycline. To help link changes to specific arrangements of the iPSCs, the cells were also engineered to fluoresce in different colors when they lost ROCK1 or CDH1.

Researchers at Gladstone tested different doses and timing of gene blockade. How changes in cell subpopulations affected the observed pattern was captured, and the BU computational scientists fed the results to a machine learning algorithm, which was hence trained to classify patterns according to their similarity and infer ways of how ROCK1 and CDH1 affect iPSC organization.

Our machine-learning model allows us to predict new ways that stem cells can organize themselves, and produces instructions for how to recreate these predictions in the lab, the studys co-first author Demarcus Briers said in a statement.

The model simulated specific experimental conditionssuch as when, where and how to add drugs to the iPSCsthat could yield unique patterns in silico. Then, the team put those suggested conditions to test.

It was successful. The researchers were able to generate concentric circles to two layers of stem cell populations in a bulls-eye pattern, they reported.

We've shown how we can leverage the intrinsic ability of stem cells to organize, Todd McDevitt, the studys senior author, said in a statement. This gives us a new way of engineering tissues, rather than a printing approach where you try to physically force cells into a specific configuration.

RELATED:Nose drop with adult stem cells restores sense of smell in mice

Stem cells are a key venue for regenerative research, either for studying disease and potential treatment or for transplant. Last year, scientists from the University of Edinburgh used 3D scaffolds made of polycaprolactone to carry embryonic stem cells and iPSCs, and successfully generated functional liver tissues that help diseased mice break down the amino acid tyrosine. A research team at the Morgridge Institute for Research recently used a drug called RepSox to help iPSCs form better smooth muscle cells as building blocks for functional arteries.

For the Gladstone-BU team, the researchers are planning to expand the model to include other genes to get an even wider pool of possible cell configurations. On top of that, rather than just making flat patterns as in this study, their goal is to design 3D shapes or organs.

We're now on the path to truly engineering multicellular organization, which is the precursor to engineering organs, said McDevitt. When we can create human organs in the lab, we can use them to study aspects of biology and disease that we wouldn't otherwise be able to.

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Applying AI and CRISPR to stem cells to improve regenerative medicine - FierceBiotech

In the 90s, Alzheimers researchers were full of optimism. New genetic studies all pointed to one culprithard clumps of protein, called amyloid, that litter the brains of people with the disease.

With the emergence of the first tangible target, pharmaceutical companies jumped in to develop drugs to clear amyloid from the brain. In animals, the drugs appeared to improve memory. But the results of human clinical trials that followed were disheartening: One after one, these drugsall designed to target amyloidhave failed to slow the disease.

The onslaught of news about these failures has left the public wondering whether amyloid has anything to do with Alzheimersand whether a new approach is needed.

The field has already begun to redirect its focus, says Scott Small, MD, director of Columbias Alzheimers Disease Research Center and theBoris and Rose Katz Professor of Neurology at Columbia University Vagelos College of Physicians and Surgeons.

Theres now reason to be cautiously optimismistic, he says, because we have uncovered new pathways that lead to the disease, and we know that they truly make a difference.

The CUIMC Newsroom spoke with Small about the current state of research into Alzheimers treatments and prevention.

In retrospect, the idea that reducing amyloid in the brainwhich all the failed drugs dois based on an incomplete picture of the disease.

To treat a disease, we need to treat whats broken. But its very difficult to find whats broken in these slowly progressive brain disorders.

One way to find whats broken is through genetics, but the first wave of genetic studies in the 80s and 90s only had the technical capabilities to investigate Alzheimers cases that run in families, those caused by a single gene.

The results of these studies all seemed to converge on one biological process: amyloid.

But these single-gene forms of Alzheimers are rareand account for maybe 2% to 3% of cases. Most cases of Alzheimers are caused by a complex interplay of many genes and the environment.

The field made the assumption that amyloid is the primary culprit in all forms of Alzheimers. It made perfect sense, because we see amyloid in all patients with Alzheimers, whether their disease is caused by a single gene or not.The amyloid finding was extremely exciting, and there was a sense that we were on the cusp of curing this devastating, horrible disease.

The amyloid hypothesis is that amyloid is the trigger of everything in Alzheimers. That seems now to be wrong.

New studies from the past decade tell us that amyloid is part of the story of Alzheimers disease, but its the smoke, not the fire. Weve learned that the single-gene and more common, complex forms of Alzheimers are not identical, though they do overlap.

Theres been a lot of backlash against the amyloid hypothesis lately, but in the 90s, it was the right idea. The pharmaceutical industry was right to jump on the amyloid bandwagon. And theyre now right to give it up, I think.

Back in the 80s and 90s, genetic tools weren't quite developed enough to address the real question we had: What genes are involved in most cases of Alzheimers disease?

Techniques have advanced and we can now answer this question. New studiesmany led by Richard Mayeux, MD[chair of neurology at Columbia]have been pointing to other processes in the brain. We also have better biological tools that can reveal the basic problem inside neurons.

Based on this research, the new consensus in the field is that there are two other pathways that cause the disease.

One involves protein trafficking, which is how proteins are shipped to different sites within a single cell. The health of neurons, more so than other cells, depends on protein trafficking in and out of one particular site: the endosome.

In Alzheimers, the flow of proteins out of the endosome is blocked, and we think that causes the other problems we see in the disease: the amyloid, the tau tangles also common in the Alzheimers brain, and the neurodegeneration. Essentially it's a plumbing problem.

Our research here at Columbia provided some early evidence for an endosomal trafficking problem in Alzheimers. And genetic studiesincluding those led by Dr.Mayeuxhave now found that some endosomal genes are linked to Alzheimers, which provides more support.

The second pathway involves microglia, which are cells in the brain that help maintain the health of neurons and help keep the spaces between neurons clear of pathogens, protein aggregates, and other cellular debris.

Recently discovered genesby Phil De Jager, MD, PhD, in our center and otherspoint us to these cells. But what exactly is wrong with the microglia is still hotly debated. We dont know if theyre working too well or not well enough, but we do know theyre not working properly.

We now, I believe, have evidence to help us understand why the first hypothesis was wrong. Scientifically, we have very good justification to argue why our new hypotheses are correct.

Were now seeing that companies are getting back into drug development because these new pathways are so compelling.

In the coming years, our biggest focus at the Alzheimers Disease Research Center at Columbia will be accelerating drug discovery. One of the most important goals is to develop new biomarkersfor the new Alzheimers pathways. These biomarkers are crucial for developing the new generation of theraputic agents.These biomarkers will be useful for enrolling patients into new anticipated clinical trials, following the logic of precision medicine.Also, just as biomarkers of amyloid were important for testing assumptions about the primacyof amyloid in the disease, these biomarkers are important for testingor potentially refutingthe new pathways.

Were also testing gene therapies and other ways to restore endosomal traffickingto see if that prevents neurodegeneration in animal models.

Frank Provenzano and Adam Brickman are developing new techniques, with imaging and cognitive testing, to detect patients with endosomal defects as early as possible. We think the sooner we can treat people, the better. Sabrina Simoes, one of our newest members, is developing new ways to use spinal fluid and blood to remotely monitor endosomal trafficking. Thats a critical step in measuring a drugs effectiveness when the drug moves to clinical testing.

In science, though, you never can be sure.The only way well know were right is by developing drugs and testing the hypothesis in clinical trials in patients, like we did with the amyloid hypothesis.

In my practice, I encounter many people who have family members with Alzheimer's and theyre worried about that their genes. But in most cases, just because your mother has it, doesnt mean youre going to get it.

In a complex disease, each gene and each environmental factor is like putting a pebble on a scale. None of them by themselves can prevent or cause Alzheimers.So if your parent has Alzheimers, that puts one pebble on the scale. But if you went to college, if you exercise, those are pebbles on the other side of the scale.

Many of the things that we thought historically cause Alzheimer's have been debunkedfor example, the idea that itwas caused by various heavy metals. But we do know that maintaining cardiac health is good: Exercise is good; smoking is bad; developing diabetes or obesity increases the risk.These recommendations, as most people know, are true for any disease.

People often ask me this question, hoping I know something that no one else does. I dont have any other answers at the moment, but everyone in the field is doing their best to find new ways to forestall this disease.

Read more from the original source:
Will a Treatment for Alzheimer's Ever Be Found? - Columbia University Irving Medical Center

When Amber Freed first told doctors her baby boy wasnt able to move his hands, they said that wasnt possible.

Freed had given birth to twins in March 2017. While her baby girl, Riley, squirmed and babbled and crawled through the first year of her life, her fraternal twin, Maxwell, was different. He didnt crawl or babble like Riley did. I would fill out their baby books each month, and Riley had met all of these milestones. Maxwell didnt reach one, she said. Most alarmingly, however, Freed noticed that he never moved his hands.

She knew the news was going to be bad when they sent her to the sad room at the hospital, a featureless conference space filled with grim-faced doctors, to hear the diagnosis.

You take your baby to the doctor and you say, He cant move his hands. And they look at you and they say, Of course he can, said Freed.

Then they look for themselves, and you can see from the look on their faces that they have never seen anything like this.

On June 14, 2018, at the Children's Hospital Colorado in Denver, Maxwell was diagnosed with a genetic disease called SLC6A1. The diagnosis explained why the infant hadnt moved his hands or learned how to speak for the first year of his life, while Riley was thriving. But it didnt explain much else: All the doctors who diagnosed Maxwell knew about the genetic disease came from a single five-page study published in 2014, the year of its discovery. It was too rare to even have a name, she was told, so the doctors just called it by the name of the affected gene: SLC6A1.

Now her 2-year-old son is at the center of a multimillion-dollar race against time, one thats come to include genetics researchers whom Freed personally recruited, paid for by $1 million that Freed and her husband, Mark, have raised themselves. At the center of their research will be specially crafted mutant mice that Freed paid scientists in China to genetically alter to have the same disease as Maxwell. The four mice are scheduled to arrive stateside next week, but Freed said shes prepared to smuggle them into the US disguised as pets if there are any problems.

In total, Amber and Mark will need to raise as much as $7 million to test a genetic treatment for their child. And unless they can find and fund a cure, SLC6A1 will condemn Maxwell to severe epileptic seizures, most likely starting before he turns 3. The seizures may trigger developmental disabilities for a lifetime, often accompanied by aggressive behavior, hand flapping, and difficulty speaking.

And the Freeds will have to do it largely alone there are only an estimated 100 other people diagnosed with SLC6A1 in the world. This is the rarest of the rare diseases, pediatric geneticist Austin Larson of the Children's Hospital Colorado told BuzzFeed News.

SLC6A1 is just one of thousands of untreatable rare diseases, and the perilous path it has set up for Freed, half science quarterback and half research fundraiser, is one that few parents can follow. My dream is to create a playbook of how I did this for those that come after me, said Freed. I never want there to be another family that has suffered like this.

You can think of SLC6A1 as a vacuum cleaner in the brain, genetic counselor Katherine Helbig of the Childrens Hospital of Philadelphia, told BuzzFeed News. Helbig will speak at the first conference on the gene at the American Epilepsy Society meeting in Baltimore on Dec. 5, an effort organized by Freed.

The protein made by the gene acts as a stop sign to message-carrying chemicals in the brain, halting them by vacuuming them up once they reach their destination brain cell, Helbig explained.

When one of the two copies of the SLC6A1 gene in every brain cell is damaged, like in Maxwells case, too little of its protein is available to perform its vacuuming duties, leading to miscommunication between cells, developmental disorders, autism-like symptoms, and, often, severe epileptic seizures.

Maxwell is about the age when epileptic seizures typically start in kids with the genetic disease, said Helbig, adding, There probably are many more children out there who have it, but they just havent had the right test to find it. At least 100 similar genetic defects cause similar kinds of epilepsy, afflicting about 1 in 2,000 kids, she said.

I was the one who presented this diagnosis to Amber, said Larson of the Children's Hospital Colorado. There was no medicine or diet or any other treatment for SLC6A1. It wasnt an easy conversation. Most of the time when we present a diagnosis for a genetic condition, there is not a specific treatment available.

At that moment, it was just vividly clear that the only option was for me to create our own miracle, said Freed. Nobody else was going to help.

Half the battle with a rare genetic disease is getting researchers interested, said Helbig.

At that moment, it was just vividly clear that the only option was for me to create our own miracle. Nobody else was going to help.

So that is what Freed set out to do. She quit her job as a financial analyst and started making phone calls to scientists, calling 300 labs in the first three months. For those who didnt respond, she sent them snacks via Uber Eats.

Her search, and a rapid-fire education on genetic diseases, led her to conclude the best hope for helping Maxwell was an experimental technique called gene therapy.

All the roads zeroed in on one scientist: Steven Gray of the University of Texas Southwestern Medical Center in Dallas. In 2018, a team headed by Gray reported the first human experiments of gene transfer by spinal injection, conducted in 5 to 10 children with mutations in a gene called GAN that causes swelling in brain cells.

The GAN gene transfer in that experiment, first tested in mice, attached a corrected version of the damaged gene to a harmless virus. Viruses reproduce by infecting cells and hijacking their DNA machinery to reproduce their own genes, making more viruses. The gene therapy virus in turn leaves behind a corrected gene in the DNA of cells they infect. Injected into the spinal cord, Grays virus can travel straight to the brain, leaving behind the corrected gene after the virus has run its course.

I gave him my 30-second equity analyst pitch. I told him why Maxwell was a good patient, that we would raise $4 million to $7 million, and quarterback every step of the research, she said. And it worked. He agreed to make it a priority if we could raise the money.

The SLC6A1 researchers with the Freeds at a science meeting. From left: Terry Jo Bichell, Frances Shaffo, Amber Freed, Katty Kang, and Mark Freed.

Less than a month after meeting Gray, Freed contacted a lab at Tongji University in Shanghai that was also researching SLC6A1. The lab agreed to develop a mouse with Maxwells specific mutation for less than $50,000, using a gene modification technology called CRISPR that has revolutionized genetic engineering in the lab. CRISPR mice are much more expensive in the US, and this lab had experience with the gene, said Freed.

By July of this year, an experiment with a gene therapy virus that corrects SLC6A1 was tested on normal lab mice, which showed no sign of a toxic response, an encouraging sign. And by September, a line of CRISPR mice with Maxwells exact genetic mutation had been created at Tongji University.

It is the literal mouse version of him, said Freed. Testing a therapy in this mouse is as close as science can get to testing in my son directly.

To pay for all this, Maxwells family started fundraising last November and organized the first medical symposium on SLC6A1 in New Orleans that same month. They opened a GoFundMe account, which has raised $600,000, and held 35 fundraisers, which raised an additional $400,000 by October. In one charity competition, Larson from the Colorado Childrens Hospital, who diagnosed Maxwell, personally helped her raise $75,000.

It is the literal mouse version of him. Testing a therapy in this mouse is as close as science can get to testing in my son directly.

That money is helping to pay for the next step getting the CRISPR mice to Grays lab to test the SLC6A1-correcting virus on them. But its not as simple as putting the mice in a box and shipping them by mail. The mice will be transferred through a lab at Vanderbilt University headed by Katty Kang, an expert on the neurotransmitter disrupted by Maxwells mutation.

Amber is helping us to advance science, and everyone is making this a priority because of the young lives at stake not just Maxwell, but other children this could help, Kang told BuzzFeed News.

Once the four mice arrive, they will spend several weeks in quarantine, be tested to make sure they have Maxwells specific point mutation in the SLC6A1 gene, and breed with normal lab mice to produce generations of mixed-inheritance mice to serve as controls in future experiments. The mutant mice will be closely monitored before they head to UT Southwestern to make sure that they demonstrate the same problems and genetics as human patients with SLC6A1 and can therefore be used in any future clinical trials of gene therapy.

Right now at UT Southwestern, results from a safety test of the gene therapy virus conducted by Grays lab on young, normal lab mice is awaiting publication. If that works out, once the Chinese mice are sent over, they will also receive the gene-correcting virus. His team will see if their symptoms improve and to what extent their brain cells accept the corrected gene.

Maxwell's brain cells seen through a microscope (left), and a sample of his cells in a petri dish.

And then, Freed just needs another $5.5 million. Half a million dollars will go to test the virus in a second SLC6A1 animal model, likely a rat, as another safety step. Two million dollars will go toward creating more of the gene-correcting virus for a human safety study if that proves to be safe. And finally, if all that works out, $3 million will be needed to conduct the experiment on Maxwell and other children next year, following the path of the GAN clinical trial led by Gray.

Its a really horrible realization that the only thing standing in the way of a cure for your 2-year-old is money, said Freed.

Freed acknowledges that she has only been able to pursue a cure for Maxwell because her family has the resources to do so which she would never have had growing up in small towns in Texas, Montana, and Colorado in a poor family affected by alcoholism. I grew up visiting my parents in rehab and knew what to say to put a family member on a 72-hour psychiatric hold by age 12, she said. She dug herself out to build a career in finance, and hoped her kids would never have to experience the struggles she did growing up.

Even so, the fight hasnt been easy on them or on Maxwells sister, Riley.

Freed worries her daughter is growing up in doctors' waiting rooms, waiting on treatments for her brother to end. Maxwells disease has progressed, causing him to constantly clench his fingers, and sometimes pull his sisters hair. His 3-year-old sister will gently remind him, Soft hands, Maxie.

Families like the Freeds are at the forefront of efforts to turn diagnoses of rare genetic ailments, which often used to be the stopping point for medicine, into treatments. A similar case saw the family of a 3-year-old girl, Mila Makovec, raise $3 million for gene therapy to cure her Batten disease, a deadly genetic brain disease that affects 2 to 4 of every 100,000 children born in the US.

In a New England Journal of Medicine editorial on that case published in October, FDA officials questioned how high the agency should set the safety bar for such treatments, meant for severe diseases affecting so few people. In these cases, parents are often collaborators in developing treatments, and might not want to stop efforts that come with high risks. Even in rapidly progressing, fatal illnesses, precipitating severe complications or death is not acceptable, so what is the minimum assurance of safety that is needed? wrote senior FDA officials Janet Woodcock and Peter Marks.

This is way beyond what anyone expects of families.

Finally, Woodcock and Marks wrote, finding sustainable funding for such interventions may prove challenging, because the cost of production can be quite substantial, particularly for gene therapies.

In our era of financial inequality, the specter of wealthy parents buying custom genetic treatments for their childrens ailments while other parents desperately resort to GoFundMe accounts, or else do nothing looms as a possibility.

This is way beyond what anyone expects of families, said Larson. The pathway has been opened up by the brave new world of improved genetic diagnoses, and the coming of age of rapid genetic engineering tools like CRISPR.

But only 20 years ago, an experimental gene therapy that relied on a harmless virus killed an 18-year-old volunteer, Jesse Gelsinger, in a research misconduct case that brought gene therapy to a standstill. Now more than 2,500 gene therapy clinical trials have been conducted, and more than 370 are underway. The human genome was not sequenced until 2000; today, mapping an entire human gene map costs around $700. In this new era, customized treatments for rare genetic diseases like Maxwells are suddenly possible.

What I hope is that we are paving the way for other parents to help their children, said Freed.

Families of children with rare genetic diseases are also working together to make treatments like the one Freed is spearheading possible, said Larson.

They support each other and work together, he said. The best example might be the families of children with cystic fibrosis, who through the Cystic Fibrosis Foundation and the discovery of the gene responsible for the disease in 1989 have pushed for the discovery of new drug treatments. In October, the FDA approved a breakthrough pharmaceutical that could treat 90% of cases.

It is easier working with FDA on this kind of approach rather than starting from scratch, Gray told BuzzFeed News by email. After all, he said, its easier to follow a path that youve already walked down.

Similarly, Freed hopes the SLC6A1 Connect advocacy group she started can lead to similar treatments for other children with genetic epilepsies caused by the gene.

I dont think any parent should be expected to single-handedly cure his or her childs rare disease, said Helbig. Amber is a very tenacious and persistent person, and she will fight tooth and nail for her kids. But a lot of people dont have the resources and they shouldnt have to.

Helbig says that cautious optimism is appropriate on the chances of research yielding a genetic therapy for children like Maxwell. For SLC6A1, its really too early to say whether this is going to work.

But if it works, it might lead many more parents to get genetic tests for children that will reveal undiagnosed problems, she said. Many doctors discourage extensive genetic tests, thinking they wont find anything helpful. In the absence of known treatments, insurers are also reluctant to pay for such tests, discouraging all but the most fortunate and resourceful parents. Even for them, there are no guarantees.

The other tough reality is the possibility this treatment wont be completed in time to help Maxwell, said Freed. I love him with every ounce of my being, and I want him to know that I did everything humanly possible to change his outcome.

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This Mom Is Buying Mutant Mice From China To Find A Cure For Her Sons Rare Genetic Disease - BuzzFeed News