Vertex Targets BAFF and APRIL to Restore Immune Balance in IgAN

Key Quotes

"A routine medical test that Rachel only took because she was pregnant showed protein in her urine that led to further tests a biopsy and eventually a phone call delivering a diagnosis it was a pretty quick conversation we know it is iga nephropathy it's a rare kidney disease there is not a cure we don't have a cause"

This quote highlights the unexpected nature of Rachel Benton's IgA nephropathy diagnosis. The author explains that a routine pregnancy-related medical test revealed protein in her urine, which then led to further diagnostic procedures. This underscores how a serious, chronic condition can be discovered through seemingly ordinary medical screenings.

"Normally the patients i see have no idea why they're coming to see a kidney doctor in many cases it starts with an asymptomatic person having a urine test like in rachel's case with a routine urine test during pregnancy perhaps you've joined a new gym you get a physical you want to get a mortgage you might have a job that requires you to have a physical and someone dips your urine and they go oh wait a minute there's blood and protein in here"

Dr. Jonathan Barratt explains that IgA nephropathy often presents without noticeable symptoms, making early detection challenging. He illustrates that the disease is frequently identified incidentally through routine urine tests performed for various reasons, such as joining a gym or applying for a mortgage. This emphasizes the importance of these standard screenings for uncovering underlying kidney issues.

"Here's what we do know about the disease so each kidney contains about a million filters and they are continually filtering the blood to generate the urine and in iga nephropathy this protein called iga starts sludging up those filters and stopping them from working properly and if the filters don't work very well they become leaky and blood and protein can appear in the urine over time sometimes months sometimes years your kidney function declines"

This quote, from Dr. Jonathan Barratt, provides a concise explanation of the pathological mechanism of IgA nephropathy. He describes how the protein IgA accumulates in the kidney filters, impairing their function and leading to leakage of blood and protein into the urine. Dr. Barratt clarifies that this process results in a gradual decline of kidney function over time.

"The big challenge is actually the impact on mental wellness because if you're a young person and i tell you you've got this disease it's incurable there's a risk it could cause kidney failure in the future but i can't tell you when you might need to go on dialysis or get a transplant but i can't tell you when that sense of uncertainty can be absolutely devastating for young people"

Dr. Jonathan Barratt points out the significant psychological toll of an IgA nephropathy diagnosis, particularly for younger individuals. He explains that the incurable nature of the disease, coupled with the unpredictable timeline for potential kidney failure, dialysis, or transplant, creates profound uncertainty. Dr. Barratt states that this lack of predictability can be devastating for patients.

"We focus on causal human biology and on human validated targets and then we ask the question what's the right approach to take and we are completely methodical we'll use whatever's the right tool in the toolbox if you like to address their biology and then to come up with a transformative therapy"

Mark Bunnage describes Vertex Pharmaceuticals' research methodology for tackling serious diseases like IgA nephropathy. He states that the company concentrates on understanding the fundamental biological causes of diseases and targets that have been validated in humans. Mr. Bunnage explains that Vertex employs a methodical approach, utilizing the most appropriate tools to address the underlying biology and develop potentially transformative treatments.

"Baff and april are two similar but distinct proteins that control the life cycle of the b cell so baff more in the early stage of development and maturation of the b cell and april more in the later stage of the b cell development all the way through to it becoming an antibody secreting cell baff and april really seem to be two of the most critical proteins driving this transition from something that would protect us to something that would actually make antibodies that will harm our native tissues"

Dr. Manish Maskey explains the roles of the proteins BAFF and APRIL in the context of B cell development and their connection to autoimmune diseases. He clarifies that BAFF influences the early stages of B cell development, while APRIL is involved in later stages, leading to antibody-producing cells. Dr. Maskey highlights that these two proteins are critical drivers in the process where B cells shift from protecting the body to producing antibodies that attack the body's own tissues.