Unfortunately very little is known about how this disease develops, so a new breakthrough published in Neuron (and by a second group also in Neuron) is reason for hope. Work by two independent groups uncovered a locus on chromosome 9 (actually an expansion of repetitive DNA in a non-coding region called C9ORF72) is implicated in at least a third of ALS cases. This sequence variation seems to affect the cells ability to recycle and cope with damaged proteins; when these proteins fail to be properly processed, the cell is damaged an ALS is the result. While this research may not explain all the causes of ALS, it is an important landmark in the battle against this illness, and provides a target for future research and therapeutic intervention.

The regions of the brain such as the hippocampus and the frontal cortex are densely populated with insulin receptors.  As well they are found in synapses in which insulin signaling participates in synaptic remodeling and synaptogenesis (1,2). In parallel insulin regulates the utilization of glucose in the hippocampus and other regions of the brain to promote optimal memory in normal metabolism (3).  In AD, it has been shown that reduced levels of insulin and insulin activity exist (4,5).  Interestingly insulin has a tight relationship to amyloid beta, a toxic peptide responsible for the onset of the disease.  Insulin can regulate the levels of amyloid beta to deliver protection from the degenerative nature of the peptide on neurons (6-8).

A pilot clinical trial published in the archives of neurology titled,  Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment, has shown insulin’ ability to be a protective new therapy in the fight against AD.  The trial hosted 104 participants, of which 30 participated in the use of a placebo, while insulin at 20IU and 40IU were delivered to 36 and 38 participants respectively.  The insulin was administered through a nasal drug delivery device for a total of 4 months. Surprisingly the 20IU and 40IU group experienced improved memory recall and preserved general cognition.

It was very important to identify a method of administration of insulin properly and direct to the brain without disrupting blood sugar levels.  When taken as a nasal spray it reaches the brain in just a few minutes with no apparent adverse affects on the body. Although a very promising study, it is still a preliminary study, more research will have to be carried out to ensure the safety and effectiveness of insulin as a therapy for longterm use against AD.

1. Chiu SL, Chen CM, Cline HT. Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 2008;58(5):708-719. PUBMED
2. Zhao WQ, Townsend M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim Biophys Acta. 2009;1792(5):482-496. PUBMED
3. McNay EC, Ong CT, McCrimmon RJ, Cresswell J, Bogan JS, Sherwin RS. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem. 2010;93(4):546-553. PUBMED
4. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 1998;50(1):164-168. FREE FULL TEXT
5. Steen E, Terry BM, Rivera EJ; et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes? J Alzheimers Dis. 2005;7(1):63-80. PUBMED
6. De Felice FG, Vieira MN, Bomfim TR; et al. Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009;106(6):1971-1976. FREE FULL TEXT
7. Gasparini L, Gouras GK, Wang R; et al. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci. 2001;21(8):2561-2570. FREE FULL TEXT
8. Lee CC, Kuo YM, Huang CC, Hsu KS. Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation. Neurobiol Aging. 2009;30(3):377-387. PUBMED

Northwestern Medicine researchers have made a major discovery that can aid in understanding and treating Alzheimer’s. These researchers have taken human embryonic stem cells and transformed them into basal forebrain cholinergic neurons, those that die in early Alzheimer’s. The technology to grow these neurons in a laboratory will enable drug testing for treatment and also testing to study why these neurons die.

Researchers have demonstrated that these newly formed neurons work just like the originals. They were transplanted into the hippocampus of mice and were shown to function normally. The neurons produced axons to the hippocampus and pumped out acetylcholine, a chemical needed to retrieve memories.

These cells can be grown indefinitely in the lab, allowing for heavy amounts of research into these cells, something that’s never been done before. Perhaps now, with these new cells, we can be one step closer to understanding and treating this disease.

A new treatment has shown itself in the form of gene therapy. Bone marrow cells can be treated with a modified and inactivated HIV virus carrying the correct message for the ALD gene and infused back into patients with adrenoleukodystrophy. The blood cells with the correct message would then be carried to the brain where ALD will be produced and utilized to improve the disease. At present HIV is the only virus that can deliver a therapeutic gene into the nucleus of non-dividing cells. Who would have thought that HIV virus could have a positive side?