FROM BEDSIDE TO BENCH

Written By: Nicholas Dang, Harvard Class of 2027

Patients don’t often get to witness research breakthroughs in their diseases — much less have a direct role in engineering their own potential therapies. For Dr. André Weinstock, Research Director of the Alport Syndrome Foundation (ASF), living with the realities and possibilities of Alport syndrome has given him a unique perspective on his role in the larger community. 

While there is a pleasing symmetry in his current position, his journey to get there has been anything but straightforward. Impelled by a childhood love for science, André pursued a PhD in Analytical Chemistry and spent 20 years in industry as a researcher. But it wasn’t until the ASF was able to financially support research that André was able to align his research with his condition full time. He credits Sharon Lagas, one of the co-founders of the ASF, as one of the reasons why the foundation is able to support research. “She ensured ASF was really set up to have a research component because if the patients [sic] didn’t do that, no one else was going to do it on our behalf.” The necessity of independently funded research rings true: over 95% of rare diseases lack FDA-approved treatments, including Alport syndrome. Thus, after spending six years as a volunteer member of the Board of Directors, André joined the ASF staff of 3 last year to lead the ASF’s research program. The foundation’s dedication to research has encouraged those affected by Alport syndrome to support its efforts. “[The community] continues to be our largest fundraising capacity — when patients, their families, their caregivers, their friends give us money, they want a cure.” Ultimately, he hopes that one day there will be “not just one, but multiple therapies to treat or even cure Alport syndrome.” 

André was diagnosed with Alport syndrome at the age of 8. He recalled attending his sister’s kidney exam when the nephrologist suddenly asked if he had trouble hearing, a seemingly random non sequitur to a symptom that had baffled André’s mother. Fortunately, the doctor was familiar with Alport syndrome and connected André’s idiopathic hearing impairment with his sister’s kidney dysfunction, resulting in a correct diagnosis. André remarked on the serendipity of his diagnosis in 1982: “At that point, [my condition] wasn’t severe enough to get support for a very thorough test for hearing impairment,” nevermind the fact that genetic testing did not even exist yet to identify the root cause. By 1994, André’s kidneys had failed and he spent two years on hemodialysis waiting for a kidney transplant.

For many rare disease patients, misdiagnosis represents a major obstacle in their journeys; a NORD study revealed that 38% of rare disease patients receive at least one misdiagnosis. While advances in sequencing technology have facilitated the diagnosis of genetic rare diseases, convincing doctors to consider genetic testing as a diagnostic tool remains a challenge. “It is estimated 100,000 patients in the United States alone have Alport syndrome. However, most of these patients have not had genetic testing done, so either they’re completely unaware … or they have had kidney diagnosis but they haven’t had genetics performed, so they’re being misdiagnosed.” One of the main challenges he identified was the preference to ascribe symptoms to more common diseases rather than considering genetic testing as a viable option.* Even though advances in sequencing technology have made it possible and affordable to sequence the genome in hours, adoption by healthcare providers has been slow. “For most adult nephrologists, they are still not thinking of genetics as something that is cheap, covered by insurance … not thinking of it as a primary diagnostic tool.” However, André expressed optimism that increasing awareness and education is the key to increasing the accuracy of diagnosis. “As we see new doctors coming up, medical schools will be teaching that you can consider genetics as a primary diagnostic tool.” By encouraging new doctors to embrace novel technologies, he hopes that diagnosing Alport syndrome will become simpler, faster, and more accurate.

Being both a patient and a scientist has also equipped André to understand the necessity of traversing the knowledge gap. Per our current understanding, Alport syndrome can be caused by mutations in any of three genes responsible for producing a certain type of collagen (collagen-IV𝛼3.4.5) necessary for kidney function. However, the intricacies quickly accumulate once you consider the three separate types of collagen-IV, the different genes involved, and non-Mendelian genetics. As André analogized the collagen building the mesh-like glomerular basement membrane to strands of steel woven into a chicken-wire mesh, thus explaining why Alport syndrome is a progressive disease resulting from years-worth of mutated “mesh” deposited, I was able to glimpse the necessary bridge that André builds: translating the disease to the terms of the patient. Building understanding among patients and caregivers of the underlying cause of the disease is an essential step toward patient treatment and community engagement. One of his current projects involves heading the ASF Alport Patient Registry, an initiative that allows patients to take an active role in advancing our understanding of Alport syndrome by submitting information about genetic test results. Ensuring that patients understand the genetic basis of Alport syndrome and what that implies for different variants empowers them to have more autonomy and contribute to the community. To that end, he expressed a desire to compile educational resources that are approachable for doctors, patients, and caregivers yet complex enough to capture the nuances of the ever-evolving field. 

Although our understanding of the science behind Alport syndrome has increased exponentially in the past decades, advancing toward a cure is slower work. André’s extensive background as a research scientist has made him familiar with the unglamorous reality of drug development. The process of identifying drug candidates, testing them, perfecting them, designing clinical trials, recruiting patients, and finally obtaining approval can take many years and millions of dollars — not to mention the challenges of making a drug scalable and accessible to patients once it is on the market. Often, a pharmaceutical partner is needed to help fund costly trials once a promising candidate has been identified. However, convincing a pharmaceutical company to invest in research for a rare disease presents a hurdle: from a financial standpoint, rare diseases have a smaller addressable market and therefore less opportunity for profit. “We provide tools that the pharmaceutical companies are looking for,” explained André, “such as data or the voice of the patient,” in order to convince them to invest in clinical trials. Such collaboration between rare disease organizations and pharmaceutical companies is a fairly common model and one that André hopes to leverage to treat Alport syndrome. 

In spite of these difficulties, the future looks bright. There are many drugs in development for Alport syndrome, and André believes that once the first on-label therapy specifically for Alport syndrome has FDA approval, the floodgates will open for novel research and increased funding. Someday, he hopes, there might even be a gene therapy-based cure. For now, he’ll continue researching and educating via his role at the Alport Syndrome Foundation, standing at the intersection of the present and the future.

 We are honored to have Dr. Weinstock as a judge for our 2025 Hackathon!