Mark Pykett, PhD, Chief Scientific Officer at PTC Therapeutics, discusses three of his company’s clinical programs, including Spinal Muscular Atrophy, Familial Dysautonomia (FD) and AADC Deficiency.
Spinal Muscular Atrophy is a genetic disease caused by mutation or deletion of the SMN1 (survival of motor neuron) gene. It affects 1 in approximately 10,000 live births and in its most severe forms is associated with a high rate of childhood mortality. SMA is characterized by progressive loss of α motor neurons, muscle weakness and atrophy.
Familial Dysautonomia (FD) is a rare genetic disorder affecting the sensory and autonomic neurons. It is caused by a splicing altering mutation in the IKBKAP gene resulting in low levels of IKAP protein, which is critical in neuronal development. Decreased expression of IKAP in certain cell types is the molecular basis for the severe, neurodevelopmental disorder.
AADC Deficiency is a rare central nervous system disorder arising from reductions in the enzyme aromatic L-amino acid decarboxylase (AADC) that result from mutations in the dopa decarboxylase (DDC) gene. This reduction leads to deficits in the neurotransmitters dopamine, norepinephrine, epinephrine, serotonin and melatonin. In the brain, AADC is responsible for the final step in the synthesis of neurotransmitters dopamine (the precursor of norepinephrine and epinephrine) and serotonin (the precursor of melatonin). Symptoms and severity of AADC Deficiency can vary depending on the type of underlying genetic mutation which abrogates AADC enzyme function. Severe forms can arise from specific DNA mutations. In its profound forms, AADC Deficiency causes severe developmental disabilities, the inability to develop any motor strength and control (global muscular hypotonia/dystonia) resulting in breathing, feeding, and swallowing problems, frequent hospitalizations, and the need for life-long care.