It is characterized by cerebellar atrophy and peripheral neuropathy. Sufferers of Type 2 have high amounts of another protein called alpha-fetoprotein (AFP), and may also have high amounts of the protein creatine phosphokinase (CPK). Mutations in the SETX gene are the cause of the disease. AOA2 shows cerebellar atrophy, loss of Purkinje cells, and demyelination. In particular, there is a failure of the cerebrocerebellar circuit in AOA2 that has been shown to be responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning. Although there is no sign of mental retardation or severe dementia, even after long disease duration, research on families with possible AOA2 have shown mild cognitive impairment as indexed by the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale. These impairments appear to be mostly due to a deficit in initiation and concept subtests,. Ataxia telangiectasia
Telangiectasias are widened blood vessels that can develop anywhere on the skin, mucous membranes, whites of the eyes, and even in the brain. Telangiectasias are associated with multiple systemic signs, the most serious of which are unusual sensitivity to ionizing radiation, excessive chromosomal breakage, and a deficiency in the immune system. Ataxia telangiectasia results from defects in the ataxia telangiectasia mutated gene, which can cause abnormal cell death in various places of the body, including brain areas related to coordinated movement of the eyes. Patients with ataxia telangiectasia have prolonged vertical and horizontal saccade latencies and hypometric saccades, and, although not all, some patients show head thrusts,.
Lomitapide , sold under the brand name Juxtapid in the US and Lojuxta  in the EU, is a medication used as a lipid-lowering agent for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals. It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate.The US Food and Drug Administration (FDA) approved lomitapide in December 2012, as an orphan drug to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in people with homozygous familial hypercholesterolemia (HoFH).In July 2013, the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adults with HoFH. Mechanism of action
Lomitapide inhibits the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.In December 2012, drug manufacturer Aegerion announced they had been approved by the FDA to as "an adjunct to a low-fat diet and other lipid-lowering treatments...in patients with homozygous familial hypercholesterolemia (HoFH)." Side effects
In a Phase III study, lomitapide led to elevated aminotransferase levels and fat accumulation in the liver. References
External links
"Lomitapide". Drug Information Portal. U.S. National Library of Medicine.