Emerging gene-therapy technology could help dogs live healthier, if not longer, lives as mans best friend.

A startup called Rejuvenate Bio launched out of George Churchs lab at Harvard Medical School (HMS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University on Thursday, with big plans to make work on gene therapy technology engineered to prevent and treat a slew of age-related diseases in dogs and extend their healthspan.

As we age, the propensity to be afflicted with disease(s) rises. But diseases are typically researched and treated individually, and the existing armamentarium of treatments does not accommodate the interconnectedness of illnesses that arise in lockstep with age. So, Harvard researchers took a macro-level approach to the problem of age-related diseases and developed a gene therapy focused on a trifecta of longevity associated genes: FGF21, Klotho and sTGFR2 which have previously been shown to be associated with increased health and lifespan benefits in mice that were genetically engineered to overexpress them.

Science hasnt yet found a way to make complex animals like dogs live forever, so the next best thing we can do is find a way to maintain health for as long as possible during the aging process, said Church in a report by the Wyss Institute.

The researchers created separate gene therapy delivery vehicles for each gene using a serotype of adeno-associated virus (AAV8) and then injected the AAV constructs into mouse models of obesity, type II diabetes, heart failure, and renal failure to assess efficacy.

The data were striking.FGF21 alone caused a complete reversal of weight gain and type II diabetes in obese, diabetic mice following a single shot, and a combination with sTGFR2 also diminished kidney atrophy by 75% in mice with renal fibrosis. The gene sTGFR2 alone and in combination with either of the other two gene therapies improved heart function in mice with heart failure, suggesting that that co-administration of FGF21andsTGFR2 could treat all four age-related conditions.

To be sure, in this initial study in mice the injected genes did not stray into the animals genomes and did not modify their natural DNA which is a concern given the existing eugenic practices prevalent in the pet industry.

Rejuvenate Bio on Thursday unveiled plans to kick off a pilot study testing the efficacy of this gene therapy technology in arresting mitral valve disease, which affects most Cavalier King Charles spaniels by age eight and causes heart failure. This pilot study will serve as a litmus test for an animal drug trial with the FDA, which tends to take about three years to complete.

If all goes well, the company hopes to expand the treatment to all canine breeds, as more than 7 million dogs in the United States suffer from mitral valve disease.

We want to get rid of the morbidities associated with aging, so dogs can be as happy and healthy as possible throughout their lives, said Rejuvenate Bios chief technology officer Noah Davidsohn, who is a former Research Scientist at the Wyss Institute and HMS. Davidsohns dog, named Bear, serves as Rejuvenates chief inspiration officer.

The first crop of FDA-approved gene therapies for humans such as Spark Therapeutics Luxturna and Novartis Zolgensma treat rare diseases. If Rejuvenates therapy is found to be safe and effective in dogs, it could open the door to similar therapies for age-related illnesses and indeed aging in humans, a field that has attracted an explosion of interest and funding.

Although early, the study in mice showed that these so-called longevity gene therapies can be combined into a single therapeutic mixture compared to the traditional paradigm that dictates different diseases necessitate multiple interventions (and arguably accumulative exposure to side-effects), the researchers concluded.

Meanwhile, the interest in treating diseases in pets if their human owners may be so inclined is on the rise, given that 67% of US households, or about 85 million families, own a pet, according to the 2019-2020 survey conducted by the American Pet Products Association.

For instance, to treat diseases like cancer in dogs surgery, chemotherapy, or radiation are existing alternatives. But targeted therapies are the next frontier. A Silicon Valley startup called the One Health Company raised $5 million last month to help figure out which human treatments can be repurposed for their canine counterparts. The company, which likened its technology to Foundation Medicines next-generation sequencing panel in an interview with STAT, helps sequence the dogs tumor and generates recommendations for treatment.

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From mice to dogs, and someday man: George Church's gene therapy concoction for aging-related diseases - Endpoints News