Nature Medicine

A report in the April issue of Nature Medicine shows that features of premature aging can be reversed in cell culture.

Hutchinson-Gilford progeria syndrome (HGPS) is a childhood condition with features that strikingly resemble the aging process. Mutations in a protein of the cell nucleus known as lamin A cause HGPS. Indeed, the nuclei of cells from people with the disease are abnormal; they have wrinkles, herniations and show functional alterations.

Now, Paola Scaffidi and Tom Misteli show that helping the protein-synthesis machinery of the cell to skip the mutation leads to a reversal of those abnormalities. By showing that defects in the nuclei of cells from people with HGPS are reversible, these researchers give rise to the possibility of developing therapies effective not only at the level of cells, but on the whole organism.

Nature Medicine

Two reports in the April issue of Nature Medicine show that RNA interference might have therapeutic effects against amyotrophic lateral sclerosis (ALS).

ALS, or Lou Gehrig disease as is often called, is characterized by the death of neurons in the spinal cord, leading to muscle wasting and motor problems. Hereditary forms of the disease are caused by mutations in a protein known as SOD1, and mice engineered to carry a copy of the human gene show symptoms similar to what is seen in people with ALS. Two teams led by Patrick Aebischer and Scott Ralph independently showed that delivering small interfering RNAs that knockdown the synthesis of SOD1 in these mice delays the onset of the disease and slows its progression.

As treatment options for people with ALS are limited, the results of these two groups open a new avenue to pursue in the fight against this debilitating disease.

Nature Medicine

Researchers have engineered a protein that could block cat allergies, according to research published in the April issue of Nature Medicine.

During an allergic response, IgE - the main type of antibody induced in allergic disease - binds to specific receptors on the surface of immune cells, triggering the release of histamine. Cross-linking the IgE receptor (called Fc epsilon RI) with another type of antibody receptor (called Fc gamma RIIb) blocks the signals triggered by IgE and prevents histamine release. In a previous study [Nat Med. 2002 8(5):518-21] Saxon and colleagues constructed a novel fusion protein containing the receptor-binding fragments of IgG and IgE and showed that this fusion could crosslink the two types of receptors and inhibit allergic inflammation in mice.

Now, the same group has found a way of tailoring the protein to block IgE responses induced only by specific allergens. Instead of linking the IgG fragment directly to the IgE fragment, they fused it with a common cat allergen. IgE induced only by the cat allergen stuck to the fusion protein, leading to crosslinking of the two types of receptors and inhibition of histamine release from immune cells. To confirm the efficacy of this strategy in vivo, the authors showed that mice treated with the fusion protein did not develop allergic airway inflammation in response to cat allergen.

This highly targeted approach is a step forward in terms of safety, as only the immune responses to the allergen will be blocked. It could also be easily adapted to other situations such as food allergies.