JULY 2024LIFE SCIENCES REVIEW8IN MY OPINIONTHE RUB: MEDICAL AFFAIRS IS FAR MORE THAN A COMMODITY IN RARE AND GENETIC DISEASEe are at the cusp of a new era in therapeutics. Rare and genetic diseases are providing targets for therapeutic intervention and increasingly yield life-changing results for patients and their families. Our tools of intervention are comprised of a spectrum of therapeutics, including oral small molecules, injectables, anti-sense oligonucleotides, gene therapies including CRISPR-Cas-9 and Prime Editing, enzyme replacement, and a host of novel delivery approaches to break barriers to delivery of the investigational product to the target site, including the eye, crossing the blood-brain barrier and beyond.We are at the dawn of a wellspring of spectacular, promising interventions. Meaningful work is happening broadly in neurologic disease, hearing loss, blindness, cancer, heart disease, kidney disease and beyond. There are many active, promising programs. Medications for familial ATTR-CM bind to the TTR protein, stabilize the condition, and stop proteins from misfolding, mitigating and slowing disease progression. Leber congenital amaurosis type 10 (LCA10) results in severe vision loss or blindness in early infancy caused by loss-of-function mutations in the centrosomal protein (CEP290) gene. Meaningful intervention would provide the protein necessary for the assembly of the connecting cilium of photoreceptors and phototransduction. The autosomal recessive gain of function requires a second hit with interferon > > , promoting increased APOL1 gene expression, activation of inflammasomes and activation of protein kinase R, electrolyte flux across plasma or intracellular membranes, endoplasmic reticulum stress, podocytopathy, arterio-nephrosclerosis, and accelerated progression to end-stage kidney disease (ESKD).The breadth and depth of opportunity to address unmet needs, treat the cause versus the consequence of conditions, change lives, and improve the quality and quantity of life are immense. In Shakespeare's `Hamlet,' when Hamlet is contemplating suicide, he By Henry David Cremisi, MD FACP, Executive Medical Director, Medical Affairs, CaidyaW
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