New findings from a UHN phase I study show that the once- and twice-weekly administration of the drug bortezomib is generally well-tolerated and holds promising findings in terms of disease response in patients. A rapid response to treatment is imperative in AL-amyloidosis to prevent organ failure and death. AL-amyloidosis is a protein conformational disorder related to multiple myeloma where the structure of certain proteins becomes mutated and abnormally deposited in organs and/or tissues.

In collaboration with international colleagues, the OCI-led study has shown that bortezomib demonstrated a good safety profile when administered once- or twice-weekly in relapsed patients with AL. These preliminary patient findings also generally show a short time to response—approximately 1.2 and 2.3 months, respectively.

“Having a rapid response, as detected through patient blood samples, is critically important for patients with AL because we need to ensure timely therapeutic benefit of treatment in terms of organ response,” comments study lead Dr. Donna Reece. “We are in critical need of treating this disease sooner. The phase two study currently underway is looking to determine precisely the activity and tolerability of bortezomib in AL.”

Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP, Vescio RA, Liu X, Elsayed YA, Cakana A, Comenzo RL. Blood. 2009 Jun 4. [Epub ahead of print]. [Pubmed abstract]. Research supported by the EURAMY project (European Community’s Sixth Framework Programme) and by the NOBEL project (CARIPLO Foundation, Milan Italy).

A recent TGRI-led study has found evidence showing that the continuous use of androgen deprivation therapy (ADT) for at least six months in older men is associated with an increased risk of diabetes and fragility fractures, explains study lead Dr. Shabbir Alibhai. ADT is a common treatment choice for men with prostate cancer, and is often administered for approximately two to three years. However, numerous adverse effects are associated with its use.

Over a six-year follow-up period, Dr. Alibhai and colleagues Drs. Neil Fleshner, Padraig Warde and Angela Cheung collected data from more than 19,000 Ontario men with prostate cancer and found strong evidence suggesting a decreased risk of stroke or sudden cardiac death with ADT.

These findings, which stem from a cohort study of a large group of men, will help clinicians to discuss the risks of ADT with their patients,” says Dr. Alibhai. “Additional studies are needed to determine whether men younger than 66 years of age will experience similar side effects of treatment as with what we saw in this group of older patients.”

Alibhai SM, Duong-Hua M, Sutradhar R, Fleshner NE, Warde P, Cheung AM, Paszat LF. J Clin Oncol. 2009 Jun 8. [Epub ahead of print]. [Pubmed abstract].

Understanding the mechanisms required for stem cells—immature cells yet to grow into a specific or defined cell type—to divide and grow into mature cells is important to developing new strategies for patient-directed research. New findings out of TGRI are doing exactly this for cardiac investigators.

“Our findings from this animal study will help us to better understand the molecular and cellular mechanisms by which adult bone marrow cells (BMCs) can develop into cardiac muscle-like cells,” comments TGRI study lead Dr. Ren-Ke Li.

Dr. Ren-Ke Li, along with colleagues from Germany and Australia, profiled different environmental conditions to show that a specific subpopulation of BMCs from mice, when in the presence of specific proteins at optimal combinations and concentrations, formed clustered groups capable of beating in a fashion similar to early heart cells. The clustered cells also expressed proteins specific to heart muscle and exhibited structural features, such as fibers, similar to those of muscle cells in the human heart.

As explained by Dr. Li, "With the improvement in transplant techniques and cell delivery by way of biomaterials, these clustered cells could one day be used to repopulate lost heart cells and restore heart cell function. Continued research is needed to fully understand the function of these beating cell clusters, and whether engraftment in the heart is possible".

Xaymardan M, Cimini M, Fazel S, Weisel RD, Lu WY, Martin U, Harvey RP, Li RK. Stem Cells. 2009 Apr 30. [Epub ahead of print]. [Pubmed abstract]. Research supported by the Heart and Stroke Foundation of Ontario and the Canadian Institutes of Health Research.

Investigators at TWRI are one step closer to understanding how blood flow and communication networks in a specific region of the brain known as the pedunculopontine nucleus (PPN) may be associated with controlling lower limb movements and gait in patients with advanced Parkinson’s Disease (PD). These findings have important implications for future treatment strategies.

Led by Dr. Antonio Strafella and colleagues Drs. Anthony Lang, Andres Lozano and Elena Moro, the team used positron emission tomography to image the blood flow in the PPN region of PD patients who had undergone deep brain stimulation—a technique using electrodes implanted in the brain to stimulate specific regions. Study findings showed changes to cerebral blood flow and brain cell activity in the regions associated with balance and motor control when deep brain stimulation was applied, including the PPN.

“These findings suggest that modulating the PPN may cause functional changes in brain networks associated with the control of voluntary lower limb movements and gait in patients with PD,” says Dr. Strafella. “Future studies are necessary to determine the exact clinical effects of deep brain stimulation in the PPN region.”

Ballanger B, Lozano AM, Moro E, van Eimeren T, Hamani C, Chen R, Cilia R, Houle S, Poon YY, Lang AE, Strafella AP. Hum Brain Mapp. 2009 May 28. [Epub ahead of print]. [Pubmed abstract]. Research supported by the Canadian Institutes of Health Research.