Search

A study identifies a mutation in the gene coding agrin AGRN which causes a congenital myasthenic syndrome. Observations reveal that the agrin mutation also drastically affects synapse function which is associated with the maintenance of neuromuscular junctions, although it does not affect the ability of agrin to stimulate the formation of postsynaptic structures.

Linkage studies are performed in families with Escobar syndrome and eight mutations are identified within the gamma-subunit gene (CHRNG) of the acetylcholine receptor (AChR). The results have shown that Escobar syndrome is an inherited fetal myasthenic disease that also affects neuromuscular organogenesis and as gamma expression is restricted to early development, patients have no myasthenic symptoms later in life.

Byline: Paul W. Wirtz (1), Jennifer Bradshaw (1), Axel R. Wintzen (1), Jan J. Verschuuren (1) Keywords: Lambert-Eaton myasthenic syndrome; autoimmunity; family; genetics; small cell lung carcinoma Abstract: Abstract. In view of the clustering of autoimmune diseases (AIDs), we studied the frequency and nature of additional AIDs in patients with the Lambert-Eaton myasthenic syndrome (LEMS) and their family members, in both small cell lung carcinoma (SCLC) related and non-tumour (NT) related cases. Additional AIDs in patients with LEMS were assessed by interviewing the patient and studying the medical record. Family histories up to second-degree family members were established by interviewing patients, controls and family members. Forty-four patients with LEMS were assessed, of whom eighteen (41%) had SCLC. In the NT group seven patients (27%) had an additional AID, in the SCLC group two (11 %) (p=0.20). Thyroid disorder (five patients) and insulin dependent diabetes mellitus (two patients) were the most common AIDs. AIDs were significantly more frequent in families of patients with NT-LEMS (64%) than in control families (27%) (p=0.002), which was not found in SCLC-LEMS (36%, p=0.53). Affected family members were linked to the NT-LEMS patient through the maternal line in all cases. In conclusion, AIDs were more frequently found in LEMS patients without a tumour and their families, which could not be shown for SCLC-LEMS. This suggests that NT-LEMS shares immunogenetic factors with other AIDs. In families of NT-LEMS, a remarkable preponderance of maternal inheritance was seen, as has been reported previously in myasthenia gravis. Author Affiliation: (1) Dept. of Neurology, J3R-166 Leiden University Medical Centre, P. O. Box 9600, 2300, RC Leiden, The Netherlands Article History: Registration Date: 01/01/2004 Received Date: 26/01/2004 Accepted Date: 03/05/2004

The comparisons of recessive inherited muscle disease in Old Danish pointing dogs with myasthenic diseases of other dog breeds and humans are presented. It has pointed toward a defect in the synthesis of the neurotransmitter acetylcholine due to decreased activity of the enzyme choline acetyltransferase.

Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T cell-regulated, antibody-mediated autoimmune diseases. The major autoantigen in MG is the nicotinic acetylcholine receptor (AChR). Two peptides, representing sequences of the human AChR [Alpha]-subunit, p195-212 and p259-271, were previously shown to be immunodominant T cell epitopes in MG patients as well as, respectively, in SJL and BALB/c mice. A dual analog (termed Lys-262-Ala-207) composed of the tandemly arranged two single amino acid analogs of p195-212 and p259-271 was shown to inhibit, in vitro and in vivo, MG-associated autoimmune responses. Furthermore, the dual analog could down-regulate myasthenogenic manifestations in mice with EAMG that was induced by inoculation of a pathogenic T cell line. In the present study, the ability of the dual analog to treat EAMG induced in susceptible C57BL/6 mice by native Torpedo AChR was evaluated. Mice that were diagnosed to have clinical symptoms of EAMG were treated with the dual analog by oral administration, 500 [micro]g per mouse three times a week for 5-8 weeks. Treatment with the dual analog down-regulated the clinical manifestations of the ongoing disease as assessed by the clinical score, grip strength (measured by a grip strength meter), and electromyography. The effects on the clinical EAMG correlated with a reduced production of anti-AChR antibody as well as a decrease in the secretion of interleukin-2 and, more dramatically, interferon-[Gamma], in response to AChR triggering. Thus, the dual analog is an efficient immunomodulator of EAMG in mice and might be of specific therapeutic potential for MG.

The article discusses the new different therapies being offered to cure Myasthenia Gravis as the current ones being offered are non-specific and can have various side effects.