Disease Areas

Lipoprotein Lipase Deficiency (LPLD)

LPLD affects only around one to two in every million people worldwide, although in certain geographic areas, such as parts of Canada, the disease is more prevalent. Symptoms include, among others, abdominal pain and patients are at very much increased risk of developing (recurrent) acute pancreatitis.

In LPLD patients chylomicrons, particles produced in the gut from dietary fats that circulate in the blood and carry around fats (triglyceride molecules), cannot be broken down and accumulate in the blood. This may result in acute pancreatitis, which is usually extremely painful, can be lethal and often necessitates intensive care.

As LPLD is an inherited disorder, genetic testing of a person with symptoms and signs generating suspicion of LPLD being present is the most reliable method of diagnosis in most cases. There are over 100 different alterations in the lipoprotein lipase (LPL) gene that can cause LPLD. Detecting these alterations involves isolating DNA from a sample of blood or saliva and examining the entire coding region of the LPL gene for abnormalities. Genetic testing can detect individuals with LPLD (people with two altered LPL genes) and those who are carriers (people with only one altered LPL gene). The parents and the children of people with LPLD are usually ‘carriers’ of the disease, and do not have symptoms of LPLD. Brothers and sisters of someone with LPLD have a 25% chance of also having the disease, and have a 50% chance of being a carrier. They also have a 25% chance of having completely ‘normal’ LPL genes. Because genetic testing may have emotional, family, and social implications, counseling is advised.

The standard disease management approach for LPLD is to reduce symptoms and the risk of pancreatitis by decreasing levels of chylomicrons (particles that carry fat around) in the blood. This may be achieved by severely restricting the fat content of the diet. Fat lowering drugs, often used in other conditions involving raised blood fat levels, are generally not effective in LPLD.

Case Study: Jill, 47 Years

Hemophilia B

Hemophilia B is a serious inherited orphan disease characterized by repeated and sometimes life threatening episodes of external and internal bleeding after accidental trauma or medical interventions. 
The episodes may cause long-term damage, for instance to the joints, and may be fatal if they occur in the brain. The defect in blood clotting in hemophilia B is caused by the lack of functional clotting Factor IX as a result of mutations in the gene encoding this protein.

Protein replacement is the current standard of care. 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, AMT’s hemophilia B gene therapy is aiming at restoring the function of blood clotting long-term through the introduction of the functional gene for the Factor IX protein into the patients’ liver cells.

 Case Study: Hajo, 58 Years

Acute Intermittent Porphyria (AIP)

AIP is a rare liver metabolic disorder resulting from 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 problems including acute, severe abdominal pain attacks, muscular weakness and an array of neurologic manifestations, including psychiatric episodes, seizures and coma. In the majority of cases, attacks are triggered by precipitating factors such as hormonal fluctuations, infections, drugs and dietary changes.

Longterm consequences may include irreversible nerve damage, liver cancer and kidney failure. Acute porphyric attacks can be life-threatening and currently available therapies do not prevent them nor their full consequences. AMT-021 is intended to provide long-term normalization of the PBGD protein in order to prevent acute attacks and their complications.

 Case Study: Amelie, 32 Years

Parkinson’s Disease (PD)

PD is a neurodegenerative disorder that affects the sufferer’s motor skills, speech, and other functions so that every action becomes increasingly difficult or eventually impossible. The symptoms are caused by degeneration and death of nerve cells in the specific part of the brain that produces dopamine, a chemical which sends messages in the brain to control movement.

At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms. The most widely used form of treatment is still 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.

AMT’s aim is to inject recombinant AAVs (see page 9) that carry the gene for GDNF into the brain.

Case Study: William, 42 Years

Duchenne Muscular Dystrophy (DMD)

DMD is a particularly severe and progressive disease that shows itself early in young children, almost exclusively boys.

The disease is caused by mutations in the dystrophin gene, which is located on the X-chromosome, thereby blocking the production of functional dystrophin protein. As dystrophin plays a critical role in muscle maintenance, the disease causes progressive weakening of all muscles. Most patients die when the heart or those muscles that control breathing no longer function adequately.

Currently there is no cure available; patients die in young adulthood.

Innovative gene therapy approaches provide the big promise of preventing this fatal disease outcome with a single treatment. AMT is developing a gene therapy product based on “exon skipping” technology which effectively bypasses the genetic defect so that functional dystrophin protein can be produced.

Case Study: Justus, 19 Years