Neuralstem announces initiation of Phase 2 trial of NSI-189 Neuralstem announced the initiation of a Phase 2 clinical trial evaluating NSI-566, the Company’s lead neural stem cell candidate, as a potential treatment for ischemic stroke. Neuralstem announced the positive topline results of Phase 1 stroke study in the 2018 ISSCR (International Society for Stem Cell Research) abstract on June 23, 2018. The trial will be taking place at Bayi Brain Hospital in Beijing, China, commencing on August 1, 2018. Managing the trial will be James Li, Ph.D., Executive Vice President of Asia Operations of Suzhou Neuralstem Ltd, a wholly owned subsidiary of Neuralstem, Inc., located in Suzhou, China. Dr. Li has been made the Manager and a Registered Agent of Suzhou Neuralstem. Neuralstem will be allocating US$3 million toward this trial.
Tuesday, July 31, 2018
Evercore ISI Downgrades resTORbio Inc. (TORC) to In Line
Evercore ISI downgraded resTORbio Inc. (NASDAQ: TORC) from Outperform to In Line with a price target of $17.00 (from $29.00).
Sanofi stockpiles drugs to prepare for hard Brexit
Sanofi has been preparing drug shortage contingency plans for over a year in the event that the U.K. fails to reach an agreement with the EU on Brexit, the Wall Street Journal reports, citing a person familiar with the matter. The move is the most recent sign that big European companies are concerned about the prospects of a hard Brexit, where the U.K. doesn’t reach a deal over its future relationship with the EU, the report notes
Google of CRISPR? Tech legends Tim Cook, Jeff Huber back Mammoth Bio
A startup led by a group of Bay Area grad students says it’s building a platform that harnesses the “search engine” function of CRISPR, winning $23 million in backing from a slew of high profile investors Tuesday.
The company, called Mammoth Biosciences, was co-founded by CRISPR legend Jennifer Doudna — one of the most famous scientific pioneers behind CRISPR/Cas9 gene editing tech. The other founders include the 29-year-old CEO Trevor Martin, a Stanford PhD, and CTO Ashley Tehranchi, also out of Stanford. The duo launched the company with the help of two students in Doudna’s lab: Janice Chen and Lucas Harrington, who will lead scientific research. Doudna heads up the scientific advisory board.
Operating under stealth mode until recently, Mammoth first stepped out this April with news that it planned to create a platform for diagnostics. With tech in-licensed from Berkeley, the company wants to apply CRISPR tech to new frontiers.
While many describe CRISPR as the “scissors” of gene editing, cutting DNA and replacing bits of genetic material where needed, Mammoth is more interested in the search function of CRISPR.
“CRISPR is biology’s search engine first,” Martin told TechCrunch in an interview. “Control + F is the exciting part. At core it’s just this amazing search engine that we can use to find things. The way that we search for things is just like Google.”
Now, Mammoth has a round of fresh capital to invest in its platform and staff. The $23 million round was led by Mayfield with participation from NFX and 8VC. Apple’s Tim Cook and the first CEO of Silicon Valley cancer screening startup Grail, Jeff Huber, also joined the round for an unspecified amount.
Blair Ups Medpace, Sees ‘Strong Biotechnology Funding Environment’
Medpace Holdings Inc MEDP 30.38% reported better-than-expected second-quarter earnings Monday afternoon.
The Analyst
William Blair’s John Kreger upgraded Medpace from Market Perform to Outperform.
The Thesis
The company reported adjusted EPS of 67 cents on an ASC 605 basis in Q2, well above Kreger’s 39-cent estimate. (See the analyst’s track record here.)
The beat came due due to better gross margins and higher revenue, the analyst said, naming the earnings beat, excellent bookings and guidance raise as the drivers behind William Blair’s upgrade.
Medpace increased 2018 guidance and said it expects higher revenue by $39 million and earnings that are 65 cents per share higher on an ASC 605 basis, Kreger said. His estimate is similar, as as he expects $40 million higher revenue and a 60-65-cent EPS increase on an ASC 605 basis.
“We view the strong biotechnology funding environment as an ongoing positive for all of the CROs, but particularly for Medpace given its larger exposure to smaller clients,” the analyst said.
William Blair expects Medpace to perform well in the second half of the year and in 2019.
Heat therapy boosts mitochondrial function in muscles
A new study finds that long-term heat therapy may increase mitochondrial function in the muscles. The discovery could lead to new treatments for people with chronic illness or disease. The study — the first of its kind in humans — is published ahead of print in the Journal of Applied Physiology.
Mitochondria, the “energy centers” of the cells, are essential for maintaining good health. A decrease in the number or function of mitochondria may contribute to chronic and potentially serious conditions such as heart disease, chronic obstructive pulmonary disease and type 2 diabetes. Exercise has been shown to create new mitochondria and improve function of existing mitochondria. However, some people with chronic illnesses are not able to exercise long enough — previous research suggests close to two hours daily — to reap the benefits. Rodent studies have suggested that heat exposure may also induce the production of more mitochondria.
Researchers from Brigham Young University in Utah studied 20 adult volunteers who had not participated in regular exercise in the three months prior to the study. The research team applied two hours of shortwave diathermy — a type of heat therapy generated by electrical pulses — to the thigh muscles of one leg of each person every day. The researchers based the six-day trial of heat on the minimum amount of exercise needed to measure changes in muscle, or about two hours each day. They designed the treatment to mimic the effects of muscle heating that occurs during exercise. The therapy sessions increased the temperature of the heated leg by approximately 7 degrees F. Each participant’s other leg served as a control, receiving no heat therapy or temperature change. The researchers looked at mitochondria content in the muscles on the first day of therapy and 24 hours after the last treatment.
Mitochondrial function increased by an average of 28 percent in the heated legs after the heat treatment. The concentration of several mitochondrial proteins also increased in the heated legs, which suggests that “in addition to improving function, [repeated exposure to heat] increased mitochondrial content in human skeletal muscle,” the research team wrote.
“Our data provide evidence to support further research into the mechanisms of heat-induced mitochondrial adaptations,” the researchers explained. People who are not able to exercise for long periods of time due to their health may benefit from [heat] treatments.
Story Source:
Materials provided by American Physiological Society. Note: Content may be edited for style and length.
Journal Reference:
- Paul Samuel Hafen, Coray N Preece, Jacob R. Sorensen, Chad R. Hancock, Robert D. Hyldahl. Repeated exposure to heat stress induces mitochondrial adaptation in human skeletal muscle. Journal of Applied Physiology, 2018; DOI: 10.1152/japplphysiol.00383.2018
Long-Term Heart Risks After Breast Cancer Therapy
Breast cancer survivors treated with older irradiation protocols remained at significant risk of treatment-related cardiovascular disease (CVD) for decades afterward, authors of a large retrospective review concluded.
Encompassing a treatment period of almost 40 years beginning in 1970, the review showed that anthracycline-containing chemotherapy plus irradiation of the internal mammary chain (IMC) was associated with a heart failure (CHF) risk nine times greater than that of women in the general population. Anthracycline therapy alone increased heart failure risk four times over that of the general population, according to Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and colleagues.
IMC irradiation also increased the risk of ischemic heart disease (IHD) and valvular heart disease (VHD), regardless of whether the radiation treatment was on the right or left side. In many instances, the CVD risk did not emerge for 20 years or more after treatment for breast cancer, they reported in the British Journal of Cancer.
“Our results are relevant to a large number of breast cancer survivors treated with older IMC regimens, who may remain at an elevated CVD risk for an extensive period,” the authors stated. “Follow-up in our study was too short to detect or reject an IHD risk increase associated with IMC irradiation during 2000 to 2009.”
“Recent studies showing improved breast cancer survival after IMC irradiation, still have insufficient follow-up to detect an increased CVD risk, which, as we report, continues into the third decade after treatment,” they noted.
An unrelated study showed a dose-dependent association between irradiation for breast cancer and the risk of injury to the left ventricle (LV) and coronary artery segments. Covering a 43-year period beginning in 1958, the data suggested that all coronary segments “are sensitive to radiation and that doses to all segments should be minimized,” Carolyn Taylor, PhD, of the University of Oxford in England, and colleagues, wrote in the Journal of Clinical Oncology.
Better Survival, New Risks
Advances in early diagnosis and treatment of breast cancer substantially improved survival over the past several decades. Radiation therapy and anthracycline-based chemotherapy have contributed to improved survival but at a recognized expense of an increased CVD risk, Van Leeuwen’s group noted.
Anthracycline-based chemotherapy has a dose-dependent association with cardiomyopathy and heart failure, although the cumulative incidence varied in prior studies. Documented heart effects of radiation therapy include IHD and VHD, and some studies have suggested the effects are dose-dependent.
Initial studies suggested the adverse heart effects of radiation therapy emerged about 10 years after exposure, but more recent analyses have shown that the risk begins to increase within 5 years of exposure, the authors continued.
Given the growing population of breast cancer survivors, investigators sought to quantify the long-term CVD risks following treatment for the disease. The analysis comprised 14,645 Dutch patients age <62, treated for early breast breast cancer during 1970 to 2009, with follow-up to 2012.
Following surgery, 56% of patients received radiation therapy alone, 3% received chemotherapy alone, 30% received both, and 11% received neither. For patients who received radiation to the breast or chest wall but not the IMC, the usual radiation dose to the heart ranged between 4 and 6 Gy until 2000 to 2009, when it decreased to about 1.5 Gy.
When the radiation field included the IMC, the typical dose to the heart ranged from 12 to 22 Gy, except for the subgroup of women who received radiation to the IMC and breast, which was associated with a heart dose of 9 Gy during 2000 to 2009.
When the IMC was not exposed, the CVD rate ratio (RR) for left-versus-right sided beast irradiation was 1.11, which failed to achieve statistical significance (95% CI 0.93-1.32). IMC irradiation at a dose range of 9-16 Gy versus right-sided breast irradiation only significantly increased the risk of total CVD, IHD, VHD, and CHF (RR 1.6-2.4). IHD risk remained elevated for at least 20 years after treatment.
Anthracycline-based chemotherapy significantly increased the risk of CHF versus the general Dutch population of women within 5 years of treatment and remained elevated at least 10 to 15 years after treatment (HR 4.18, 95% CI 3.07-5.69). The combination of IMC irradiation plus anthracycline-based chemotherapy increased CHF risk more than nine-fold versus women exposed to neither treatment (HR 9.23, 95% CI 6.01-14.18).
The study had some limitations including the potential for unreported CVD events.
Higher RT Doses, Higher Risk
Taylor’s group analyzed the association between radiation therapy and CVD risk in 456 women who received radiotherapy for breast cancer from 1958 to 2001 and who subsequently had major coronary events. Radiation dose to five LV segments could be estimated for 414 patients. Additionally, radiation dose to six coronary segments was estimated for a subgroup of 133 patients who had documented coronary artery disease associated with ≥70 stenosis.
Of the 414 patients with LV injury, 243 had left-sided breast cancer and 171 had right-sided cancer (RR 1.42, 95% CI 1.17-1.73), reflecting a higher typical LV radiation dose in left-sided cancer, the authors noted.
For the five segments assessed, the ratios for left-versus-right sided radiotherapy were 0.94 for inferior (95% CI 0.70-1.25); 1.42 for lateral (95% CI 1.04-1.95); 2.09 for septal (95% CI 1.37-3.19); 1.85 for anterior (95% CI 1.39-2.46); and 4.64 for apex (95% CI 2.42-8.90). Corresponding radiation dose differences for the five segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy (P<0.001 for trend).
For the subgroup of women with coronary artery disease, the ratios for left-versus-right radiotherapy for the six segments evaluated were 0.48 for proximal right coronary artery (95% CI 0.26-0.91); 1.69 for mid/distal right coronary (95% CI 0.85-3.36); 1.46 for proximal circumflex (95% CI 0.72-2.96); 1.11 for distal circumflex (95% CI 0.45-2.73); 1.89 for proximal left anterior descending (95% CI 1.07-3.34); and 2.33 for mid/distal left anterior descending (95% CI 1.19-4.59). The corresponding left-minus-right radiation dose differences were -5.0, -2.5, 1.6, 3.5, 9.5, and 38.8 Gy (P=0.002 for trend).
“For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized,” the authors concluded.
They noted a study limitation was that “individual CT information was unavailable because the women were irradiated before the era of three-dimensional CT radiotherapy planning. Therefore, it was necessary to estimate cardiac doses retrospectively using a typical CT scan.”
The study by Van Leeuwen’s group was supported by the Dutch Cancer Society, Cancer Research UK, the British Heart Foundation Centre for Research Excellence, Oxford, the UK Medical Research Council, and the British Heart Foundation to the Oxford University Clinical trial Service Unit.
Van Leeuwen and co-authors disclosed no relevant relationships with industry.
The study by Taylor’s group was supported by Cancer Research UK, the University of Oxford under the Department of Health Policy Research Programme, the UK Medical Research Council, the British Heart Foundation to the Oxford University Clinical Trial Service Unit, and by the British Heart Foundation Centre for Research Excellence at the University of Oxford.
Taylor disclosed no relevant relationships with industry. One or more co-authors disclosed relevant relationships with AstraZeneca, Atossa Genetics, and Celgene.
Primary Source
British Journal of Cancer
Secondary Source
Journal of Clinical Oncology
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