Disease AreasHemophilia B
Hemophilia B is a serious inherited orphan disease characterized by insufficient production of Factor IX, a blood clotting factor. The deficient blood clotting in Hemophilia B is caused by the lack of functional clotting Factor IX as a result of mutations in the gene responsible to encoding that essential protein.
The clinical manifestations are repeated and sometimes life threatening episodes of external and internal bleeding after accidental trauma or medical/odontological interventions. Episodes may be fatal if occuring in the brain; and repeated episodes may cause long-term damage to the joints and vital organs.
Current standard treatment is protein (Factor IX) replacement. Frequent intravenous administrations of recombinant Factor IX are required to stop or prevent bleeding. However, protein replacement therapy is costly, cumbersome, and does not completely prevent bleeding.
Administered once, uniQure’s Hemophilia B gene therapy aims to permanently restore the function of blood clotting through the introduction of the functional gene for the Factor IX protein into the patients’ liver cells. uniQure holds the rights to the Factor IX gene from St Jude’s Children Research Hospital, Memphis Tennessee. In a Phase I AAV8 gene therapy trial carried out over the last 2 years it has been demonstrated that patients experienced a sustained effect of a significant reduction of the frequency or a complete stop of prophylactic treatment. Early 2013 uniQure will start the next Phase I/II trial based on AAV5.
Acute Intermittent Porphyria (AIP)
AIP is an inherited rare metabolic disease characterized by mutations in the PBDG gene, which encodes for the enzyme porphobilinogen-deaminase, a liver protein necessary for the production of heme. Insufficient activity of this protein leads to an accumulation of toxic metabolites resulting in a wide variety of negative health consequences, including severe acute abdominal pain attacks, muscular weakness and an array of neurologic manifestations, including psychiatric episodes, seizures and coma. Long-term consequences of frequent and repeated porphyria attacks include irreversible nerve damage, liver cancer and kidney failure.
Acute porphyria attacks can be life-threatening. Currently available therapies are unable to prevent the attacks and their clinical consequences. AMT-021 is intended to provide long-term normalization of the PBGD protein in order to prevent acute attacks and their complications.
uniQure together with its partner, the University of Navarra, is recruiting patients in a preparation trial and will start the first Phase I trial in 2012.
Parkinson’s Disease (PD)
PD is a neurodegenerative disorder that progressively deteriorates motor skills, speech, and other neurological functions. In PD patients, every daily action becomes increasingly difficult and eventually impossible. The symptoms are caused by degeneration and death of neurons in the specific centres of the brain that produce dopamine, a neurotransmitter that interacts with other motor neurons in the brain in order to coordinate and control muscular action and movements.
Currently, there is no cure for PD. Medications and/or surgery can provide certain relief from major disrupting symptoms. The most widely used form of treatment is L-dopa in various forms, which is converted to dopamine in the central nervous system. From previous studies – preclinical and clinical – there is a consistent line of evidence that the infusion of GDNF protein into the brain is effective in PD. GDNF stimulates the formation of dopamine and prevents further degeneration of dopaminergic neurons.
uniQure’s aim is to administer recombinant AAV (adeno-associated virus) vector that carries the gene for GDNF to the brain. uniQure is also exploring applications of GDNF in Multiple Systems Atrophy, Huntington’s and hearing loss.
Sanfilippo Syndrome or Mucopolysaccharidosis type III (MPSIII), is a rare lysosomal storage disorder (LSD) which affects between 0.7 and 1.8 per 100,000 live birth (0.73 in France and 1.7 in England) and in which an autosomal recessive genetic defect results in the accumulation of partially degraded oligosaccharides of heparan sulfate.
uniQure together with its partner Institut Pasteur is developing a gene therapy for Sanfilippo B, or mucopolysaccharidosis type IIIB (MPSIIIB), one of four subtypes In the absence of lysosomal sulfamidase, α-N-acetylglucosaminidase (NaGlu), partially degraded oligosaccharides accumulate at toxic levels.
The clinical manifestations are mainly neurological with early symptoms observed during the first 5 years of age, leading to a progressive deterioration of cognitive abilities. Affected children require specific care after the age of 7 and progressively develop profound mental retardation with reduced somatic manifestations. Death frequently occurs at the median age of 15.
There is currently no available treatment for Sanfilippo syndrome.
It is uniQure’s aim to directly administer the gene therapy and provide a long lasting effect.